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[(\).)-262.5(H)14(o)0(w)19.3(e)0(v)20.6(e)0(r)22.1(,)-271.3(s)11.9(o)0(m)17(e)-264.3(re)16.1(p)12.8(o)0(r)16.6(t)15.6(s)-268.6(h)0(a)19.1(v)0(e)]TJ -13.654 -1.2055 TD [(i)-8.5(m)0(p)-16.7(l)-6.6(i)-8.5(c)-7.7(a)-10.6(t)-8.3(e)-7.7(d)-464.7(t)-8.3(h)-12.1(at)-472.4(t)-8.3(h)0(e)-473.3(m)0(a)-16.1(c)-7.7(r)-12(o)-7.3(ph)-17.2(ag)-12.1(e)-467.2(p)-11.1(o)-7.2(p)-11.1(ul)-11.8(a)-10.6(t)-8.3(i)-8.5(o)-7.3(n)-8(s)-465.5(a)-10.6(r)0(e)-473.2(i)-8.5(n)-8(v)-7.5(o)-7.3(l)-6.6(v)-13.4(e)-7.7(d)-464.7(i)-8.5(n)]TJ 0 -1.2114 TD [(h)11.8(e)0(l)21.5(m)0(i)15.7(n)0(t)19.5(h)11.8(-)13.8(g)0(e)20.6(n)0(e)14.1(r)11.9(a)13.3(t)0(e)19.8(d)-231.9(pr)18.7(ot)20.2(ec)20.4(ti)18.9(on)-218.2(a)13.3(g)0(a)17.8(i)0(n)19.2(s)11.9(t)-229.1(i)0(n)19.2(t)0(e)19.8(s)11.9(ti)18.9(na)17.2(l)-227.4(p)12.7(at)16.9(h)11.8(o)0(l)21.9(o)0(g)21.1(y)-234.2(\()]TJ 0 0 0 0.7 k 23.3992 0 TD (7)Tj /F13 1 Tf 0 0 0 1 k 0.4714 0 TD (?)Tj /F11 1 Tf 0 0 0 0.7 k 0.5013 0 TD (9)Tj 0 0 0 1 k 0.4655 0 TD (\).)Tj -23.5722 -1.2114 TD [(M)13.7(a)0(c)17.5(r)11.9(op)17.4(h)11.8(a)0(g)17.8(e)0(s)-180.8(a)0(r)19.2(e)-192.7(a)-195.6(v)0(e)20.6(r)11.9(s)11.9(a)0(t)16.9(i)0(l)20.7(e)-192.7(ce)20.4(ll)-186.3(p)12.7(o)0(p)17.4(u)12.8(la)18.6(ti)24.9(on)-188.3(t)15.6(h)0(a)19.1(t)-193.3(pl)18.1(a)13.3(y)0(s)-186.5(v)0(i)19.8(t)0(a)22.9(l)-191.6(ro)16.6(le)21.5(s)]TJ -1.2651 -1.2114 TD [(in)-320.9(cl)21.5(ea)17.5(r)11.9(i)0(n)19.2(g)-329.7(ba)23.9(ct)19.8(er)22.1(ia)-323.5(fr)22.4(om)-317.2(lo)16(ca)23.5(l)-328.9(t)0(i)18.9(s)11.9(su)18.7(es)22.1(,)-331(t)0(r)21.5(a)0(n)17.2(s)11.9(la)18.6(ti)18.9(ng)-319.9(a)13.3(l)0(e)21.5(r)0(t)-318.7(s)0(i)15.3(g)0(n)20.3(a)13.3(ls)-317(to)]TJ T* 0.0314 Tc [(other)-475.9(i)-1(mmune)-477.6(cells,)-478.7(s)1.5(ecretin)5.5(g)-483.3(c)-0.2(yt)5.2(oki)5(n)-0.5(es)-481.8(to)-477.1(establish)-481.9(l)0.9(ocal)]TJ T* 0 Tc [(h)11.8(o)0(m)17(e)0(o)20.8(s)11.9(ta)22.9(ti)18.9(c)-425.4(i)0(m)21.7(m)12.3(un)16.7(e)-419.5(c)0(e)20.4(l)0(l)-413.1(n)0(e)20.1(t)0(w)18.2(o)0(r)22.6(k)11.6(s,)-414.6(an)17.2(d)-422.9(p)12.8(ar)19.2(ti)18.9(ci)19.6(p)12.8(a)0(t)16.9(i)15.3(ng)-415.3(in)-410.4(T)-424.4(c)0(e)20.4(l)0(l)]TJ T* [(re)16.1(st)15.5(im)15.7(ul)12.1(at)16.9(io)14(n)-431.7(a)0(n)17.2(d)-434.8(ma)13.7(in)13.3(te)19.8(na)11.2(nc)14.1(e)-431.4(w)0(i)12(t)0(h)21.4(i)0(n)-428.3(t)0(h)15.4(e)-437.4(la)18.6(mi)15.7(na)-430.4(pr)18.7(op)11.5(ia)-424.9(\()]TJ 0 0 0 0.7 k 24.163 0 TD (10)Tj 0 0 0 1 k 0.9429 0 TD (\).)Tj -25.1059 -1.2055 TD [(A)12.7(c)0(t)19.8(i)0(v)19.8(a)0(t)16.9(e)0(d)-418.7(m)12.3(a)13.3(c)0(r)16.1(o)0(p)23.4(h)0(a)19.1(g)0(e)20.6(s)-429.7(a)13.3(r)0(e)-419.5(f)0(u)17.3(n)0(c)20.1(t)0(i)18.9(o)0(n)20.5(a)13.3(ll)22.6(y)-431.2(d)12.7(iv)19.8(id)16.1(ed)-412.7(in)19.2(to)-421.4(t)15.6(w)0(o)-416.4(m)0(a)19.7(i)0(n)]TJ 0 -1.2114 TD [(ca)17.5(t)15.6(e)0(g)14.7(o)0(r)22.6(i)0(e)19.6(s)11.9(:)-134.1(t)0(h)21.4(e)-127.1(M1)-122(ty)20(pe)-120.3(\(t)18.4(h)11.8(e)-133(cl)21.5(as)19.2(s)11.9(i)0(c)19.6(a)0(l)18.6(-)13.8(ac)17.5(ti)18.9(va)23.7(te)19.8(d)-130.5(m)0(a)19.7(c)0(r)16.1(o)0(p)23.4(h)11.8(ag)17.8(e\))-118.2(an)17.2(d)-130.5(t)0(h)21.4(e)]TJ T* [(M2)-301(ty)20(p)12.7(e)-312.1(\(t)18.4(h)11.8(e)-312.1(al)18.6(te)19.8(r)11.9(n)0(a)17.2(t)0(i)24.9(v)0(e)14.7(l)0(y)-300.5(a)13.3(ct)19.8(iv)19.8(at)22.9(ed)-305.3(m)12.3(a)0(c)17.5(r)11.9(op)17.4(h)11.8(a)13.3(ge)14.7(\))-307.5(\()]TJ 0 0 0 0.7 k 20.1528 0 TD (11)Tj 0 0 0 1 k 0.9369 0 TD [(\).)-304.3(A)12.7(l)0(t)20.9(h)11.8(ou)17.4(gh)]TJ -21.0897 -1.2114 TD [(M1-type)-447.1(macrophages)-450.1(release)-452.1(proin)]TJ /F12 1 Tf 14.8654 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammatory)-449.2(cytokines)-449.3(and)]TJ -15.3966 -1.2114 TD [(en)20.1(h)11.8(a)0(n)17.2(c)0(e)-361.5(i)0(n)]TJ /F12 1 Tf 4.3922 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(am)19.7(ma)19.7(to)20.2(r)11.9(y)-377.5(r)11.9(e)0(s)22.1(p)0(o)17.4(n)0(s)21.8(e)0(s)22.1(,)-378.8(t)15.6(h)0(e)16(y)-371.5(a)13.3(l)0(s)17.2(o)-371.3(ca)17.5(u)12.8(s)0(e)-365.8(i)0(n)19.2(j)0(u)24(r)0(y)-365.6(t)0(o)-361.7(h)11.8(os)22.6(t)]TJ -4.9114 -1.2114 TD -0.0119 Tc [(t)-11.9(i)7(ssu)-11.9(e)-341(\()]TJ 0 0 0 0.7 k 2.8466 0 TD -0.0135 Tc (12)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc [(\).)-322.2(On)-325.3(th)21.4(e)-335.9(c)0(o)20.9(n)0(t)19.5(r)0(a)19.2(r)11.9(y,)-326.6(M2)21.3(-t)17.5(yp)23.2(e)-335.9(m)0(a)19.7(c)0(r)16.1(o)0(p)23.4(h)11.8(ag)17.8(es)-324(r)11.9(e)0(l)15.5(e)0(a)23.5(s)0(e)-324(a)0(n)17.2(t)0(i)18.9(-)]TJ -3.7835 -1.2055 TD 0.0264 Tc (in)Tj /F12 1 Tf 0.8534 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0262 Tc [(ammatory)-476.6(cytokines)-475.1(a)-2.3(nd)-474.3(help)-480.2(maintain)-477.1(tissue)-476.8(immune)]TJ -1.4084 -1.2114 TD 0 Tc [(h)11.8(o)0(m)17(e)0(o)20.8(s)11.9(ta)22.9(si)15.3(s)11.9(,)-360.9(th)15.4(u)12.7(s)-364.1(av)17.8(oi)20(d)12.7(i)0(n)19.2(g)-365.5(ov)21.1(er)22.1(ac)17.5(t)15.6(i)0(v)19.8(e)-365.8(in)]TJ /F12 1 Tf 16.1783 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(am)19.7(m)12.3(a)0(t)16.9(i)0(o)20(n)-360.1(\()]TJ 0 0 0 0.7 k 4.7264 0 TD (13)Tj 0 0 0 1 k 0.9369 0 TD (,)Tj 0 0 0 0.7 k 0.5848 0 TD -0.0135 Tc (14)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc [(\).)-352.1(In)]TJ -23.8826 -1.2114 TD [(th)21.4(e)]TJ /F12 1 Tf 1.5576 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(gh)22.2(t)-330.6(a)0(g)17.7(a)13.3(in)19.2(s)11.9(t)-330.6(fo)21.2(r)11.9(e)0(i)19.6(g)0(n)-319.9(p)0(a)20.1(t)0(h)21.4(o)0(g)21.1(e)0(n)20.1(s)0(,)-319.1(t)0(h)15.4(e)-324(sh)17.8(if)19.9(ti)18.9(ng)-313.9(ba)18(la)18.6(nc)20.1(e)-330(b)0(e)20.8(t)15.6(we)18.8(en)]TJ -2.0767 -1.2114 TD [(pr)18.7(oi)20(n)]TJ /F12 1 Tf 2.1364 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(am)19.7(m)12.3(a)0(t)16.9(o)0(r)22.6(y)-335.7(M1)-330.8(a)13.3(n)0(d)-329.5(w)0(o)19.3(u)12.7(nd)16.7(-)13.8(h)11.8(ea)17.5(li)20.7(ng)-325.8(M2)-330.8(m)12.3(a)0(c)17.5(r)11.9(op)23.4(ha)19.1(ge)20.6(s)-340.2(o)0(v)21.1(e)0(r)]TJ -2.6556 -1.2114 TD [(ti)18.9(m)12.3(e)-389.6(is)-384.5(es)22.1(se)16.1(nt)19.5(ia)22.7(l)-388.5(f)0(o)15.2(r)-387.9(pr)18.7(op)17.4(er)-377.7(re)16.1(s)11.9(o)0(l)21.9(u)0(t)16.4(i)15.3(on)-385.3(of)-378.7(in)]TJ /F12 1 Tf 17.6404 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(am)19.7(ma)19.7(ti)18.9(on)-379.3(\()]TJ 0 0 0 0.7 k 4.7562 0 TD (15)Tj 0 0 0 1 k 0.9369 0 TD [(\).)-381.9(In)]TJ -23.8527 -1.2114 TD [(ad)20.1(di)22.1(ti)18.9(on)20.5(,)-331(M)0(2)21.3(-)0(t)17.5(y)0(p)23.2(e)-330(m)12.3(a)0(c)17.5(r)11.9(op)17.4(h)11.8(a)0(g)17.7(e)0(s)-318.1(h)11.8(av)17.8(e)-330(b)0(e)20.8(e)0(n)-320.1(r)11.9(ep)17(or)22.6(te)19.8(d)-327.4(t)0(o)-319.9(a)0(t)22.9(t)0(e)19.8(n)0(u)16.7(a)13.3(te)]TJ T* [(experi)9.2(mentally)-436.9(induced)-441.3(in)]TJ /F12 1 Tf 10.7716 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammati)10.5(on)-445(in)-446.2(the)-445.8(gut)-444.7(\()]TJ 0 0 0 0.7 k 9.5423 0 TD (16)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-447.5(Passiv)10.2(e)]TJ -21.7998 -1.2055 TD [(tr)21.5(an)17.2(s)11.9(f)0(e)20.7(r)-429.7(of)]TJ /F14 1 Tf 4.6428 0 TD [(in)-422.4(v)13.3(i)0(t)17(r)11.9(o)]TJ /F11 1 Tf 3.4493 0 TD [(de)17(r)11.9(i)0(v)19.8(e)0(d)-418.7(a)13.3(lt)20.9(er)16.1(na)23.2(ti)18.9(ve)20.6(ly)-419.9(a)13.3(c)0(t)19.8(i)0(v)19.8(a)13.3(te)19.8(d)-428.9(m)0(a)19.7(c)0(r)16.1(o)0(p)23.4(h)11.8(ag)17.8(es)]TJ -8.0921 -1.2114 TD 0.0259 Tc [(conferred)-474.6(s)2(igni)]TJ /F12 1 Tf 6.5465 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0259 Tc [(cantly)-476.9(reduced)-474.6(coloni)5.4(c)-477.1(i)-0.5(n)]TJ /F12 1 Tf 11.255 0 TD 0 Tc ()Tj /F11 1 Tf 0.555 0 TD 0.0267 Tc [(amma)4.2(tion)-470.7(\()]TJ 0 0 0 0.7 k 5.1501 0 TD 0.0283 Tc (16)Tj 0 0 0 1 k 1.0085 0 TD 0.027 Tc (\).)Tj -25.0701 -1.2114 TD 0.0352 Tc [(He)3.6(l)4.7(m)-0.2(in)3.3(th-m)5.8(od)6.2(ul)4.7(ate)3.6(d)-483.2(ma)6.7(cr)5.3(op)6.2(ha)6.7(ge)3.6(s)-484(h)5.2(av)3.9(e)-479.8(b)4.1(ee)3.6(n)-480.1(e)3.6(xpl)4.7(o)-1.9(r)5.3(e)-2.3(d)-477.2(a)0.8(s)]TJ T* 0 Tc [(pr)18.7(om)23(is)21.3(in)19.2(g)-234.2(t)15.6(he)16(r)11.9(a)0(p)20.1(e)0(u)17(t)0(i)24.9(c)-234.5(fo)21.2(r)-226.8(i)0(n)]TJ /F12 1 Tf 10.9865 0 TD ()Tj /F11 1 Tf 0.5192 0 TD [(am)19.7(ma)19.7(to)20.2(ry)-222.3(d)12.7(i)0(s)15.3(e)0(a)23.5(s)11.9(e)-234.5(\()]TJ 0 0 0 0.7 k 7.567 0 TD (8)Tj 0 0 0 1 k 0.4655 0 TD (,)Tj 0 0 0 0.7 k 0.4476 0 TD (16)Tj /F13 1 Tf 0 0 0 1 k 0.9369 0 TD (?)Tj /F11 1 Tf 0 0 0 0.7 k 0.5013 0 TD (18)Tj 0 0 0 1 k 0.9369 0 TD (\).)Tj -21.0957 -1.2114 TD [(Th)23.1(e)-204.6(p)0(r)18.7(o)0(g)21.1(r)0(a)19.2(m)0(m)18.7(e)0(d)-197.9(c)0(e)20.4(l)0(l)-192.3(d)0(e)17(a)0(t)22.9(h)0(-)19.7(1)-207.3(\(P)21.8(D-)20.8(1\))-198.5(is)-199.5(a)-201.5(m)0(e)16.6(m)12.3(be)20.8(r)-208.9(o)0(f)-193.7(t)0(h)21.4(e)-210.6(CD)24.4(28)]TJ -1.2651 -1.2114 TD [(s)11.9(u)0(p)19.5(e)0(r)16.1(f)0(a)23.8(m)0(i)15.7(l)0(y)-211(t)0(h)21.4(a)0(t)-215.8(d)12.7(el)21.5(iv)19.8(er)16.1(s)-220.8(n)0(e)20.1(g)0(a)17.7(t)15.6(iv)19.8(e)-222.5(s)0(i)15.3(g)0(n)20.3(a)13.3(ls)-215.5(u)12.7(p)0(o)17.4(n)-222.9(in)19.2(te)19.8(r)11.9(a)0(c)17.5(t)0(i)24.9(o)0(n)-218.2(w)14.6(it)18.9(h)-220.9(i)0(t)18.9(s)]TJ 9.5 0 0 9.5 306.1417 615.6282 Tm [(tw)24.2(o)-281.8(l)0(i)20.6(g)0(a)17.7(n)0(d)22.6(s)11.9(,)-283.3(P)13(D-)20.8(L1)-273(a)13.3(n)0(d)-269.8(P)0(D)19.9(-)0(L)19.7(2)0(.)-269.8(E)0(x)21.5(p)0(r)18.7(e)0(s)16.1(s)11.9(io)20(n)-276.6(o)0(f)-271.2(P)0(D)19.9(-)0(1)-271(o)0(n)-265.9(T)-281.2(ce)20.4(ll)22.6(s,)-271.4(B)]TJ T* [(ce)20.4(ll)22.6(s,)-193.8(m)12.3(a)0(c)17.5(r)11.9(op)17.4(h)11.8(a)13.3(ge)14.7(s)11.9(,)-199.7(an)17.2(d)-202.1(d)12.7(en)20.1(dr)18.7(it)18.9(ic)-189.3(ce)20.4(ll)22.6(s)-202.9(\()0(D)21.7(C)0(s)17.4(\))-200.1(is)-187.6(in)19.2(du)19.5(ci)19.6(bl)21.9(e)-204.6(\()]TJ 0 0 0 0.7 k 22.4324 0 TD -0.0135 Tc (19)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc [(\))14.8(.)-205.7(Th)23.1(e)]TJ -23.3693 -1.2114 TD [(PD)-10(-)-10(1)-463.9(pa)-9.8(t)-8.3(h)0(w)-9.4(a)-10.6(y)-461(i)-8.5(s)-459.5(v)-7.5(i)-8.5(t)-8.3(al)-464.8(f)-7.4(o)-7.3(r)-465.5(p)0(h)-11.2(y)-7.5(si)-14.5(ol)-7.9(o)-7.2(g)-7.5(i)-8.5(c)-461.2(re)-13.7(g)-7.5(u)0(l)-11.8(a)0(t)-12.9(i)-8.5(o)-7.2(n)-461.6(o)-7.3(f)-460.9(i)-8.5(m)0(m)-11.1(u)0(n)-13.2(e)]TJ 0 -1.2055 TD [(r)11.9(e)0(s)16.1(p)12.8(on)20.5(se)16.1(s)-292.4(t)0(o)-284.1(a)13.3(vo)15.1(i)15.3(d)-297.6(in)19.2(ju)24(ri)15.3(ou)23.4(s)-298.4(o)0(v)21.1(e)0(r)22.1(a)0(c)17.5(t)0(i)24.9(v)0(e)-289.7(i)15.3(n)]TJ /F12 1 Tf 16.3812 0 TD ()Tj /F11 1 Tf 0.5252 0 TD -0.0133 Tc [(am)-13.3(m)5.4(a)-13.3(t)9.6(i)-13.3(o)6.7(n)-307.8(\()]TJ 0 0 0 0.7 k 4.6548 0 TD 0 Tc (20)Tj 0 0 0 1 k 0.9369 0 TD (,)Tj 0 0 0 0.7 k 0.5132 0 TD (21)Tj 0 0 0 1 k 0.9369 0 TD [(\).)-286.4(In)]TJ -23.9482 -1.2114 TD [(a)13.3(d)0(d)19.5(i)0(t)18.9(i)0(o)20(n)0(,)-195.8(P)13(D-)20.8(1)-201.3(s)0(e)16.1(r)11.9(ve)20.6(s)-202.9(a)0(s)-195.6(a)13.3(n)-205(i)0(m)21.7(p)0(o)17.4(r)11.9(ta)16.9(nt)-189.4(im)21.7(mu)19.1(ne)-194.8(ch)22(ec)14.4(k)11.6(p)12.7(oi)20(nt)-195.4(to)-188.6(ke)15.8(ep)]TJ T* [(im)21.7(mu)19.1(ne)-391.7(ba)23.9(la)18.6(nc)20.1(e)-401.6(a)13.3(nd)-395.1(p)12.8(r)11.9(ev)20.6(en)14.1(t)-396.2(a)0(u)20.1(t)0(o)20.2(i)0(m)21.7(m)0(u)19.1(n)0(i)19.2(t)0(y)-391.8(\()]TJ 0 0 0 0.7 k 18.6251 0 TD (21)Tj /F13 1 Tf 0 0 0 1 k 0.9369 0 TD (?)Tj /F11 1 Tf 0 0 0 0.7 k 0.5013 0 TD (23)Tj 0 0 0 1 k 0.9369 0 TD [(\).)-393.8(A)12.7(l)0(t)20.9(h)11.8(ou)17.4(gh)]TJ -21.0002 -1.2114 TD [(m)12.3(a)0(n)17.2(y)-276(s)11.9(t)0(u)16.4(d)12.8(ie)19.6(s)-280.5(h)11.8(a)13.3(v)0(e)-271.8(s)11.9(h)11.8(o)0(w)19.3(n)-276.6(th)21.4(e)-276.2(i)0(m)15.7(p)12.8(or)22.6(ta)16.9(nc)20.1(e)-276.2(o)0(f)-265.3(P)0(D)19.9(-)0(1)-265(i)0(n)-267.2(m)0(o)17(d)12.8(ul)18.1(a)13.3(t)0(i)18.9(n)0(g)]TJ T* [(th)21.4(e)-258.3(T)-263.2(ce)20.4(ll)-246(fu)17.3(nc)20.1(ti)18.9(on)20.5(,)-259.4(s)11.9(om)17(e)-258.3(e)0(v)20.6(i)0(d)22.1(e)0(n)20.1(c)0(e)-254.1(h)11.8(as)-249.3(em)16.6(er)22.1(ge)20.6(d)-261.8(t)0(h)21.4(a)0(t)-251.6(P)13(D-)20.8(1)-261(p)12.8(la)18.6(ys)-252.2(a)]TJ T* [(d)12.7(i)0(s)15.3(t)15.6(in)19.2(ct)-218.9(ro)16.6(le)-217.2(in)-219.5(t)15.5(h)0(e)-222.7(r)11.9(eg)20.6(ul)18.1(a)13.3(t)0(i)18.9(o)0(n)-218.2(o)0(f)-217.5(m)0(a)19.7(c)0(r)16.1(o)0(p)23.4(h)11.8(ag)17.8(e)-228.5(p)12.7(ol)16(a)13.3(r)11.9(iz)19.6(at)16.9(io)20(n)-228.8(\()]TJ 0 0 0 0.7 k 22.7905 0 TD -0.0135 Tc (24)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc (,)Tj 0 0 0 0.7 k 0.4416 0 TD (25)Tj 0 0 0 1 k 0.9429 0 TD -0.0148 Tc (\).)Tj -25.1119 -1.2114 TD 0.0241 Tc [(Expression)-473.3(of)-472.6(PD-1)-475.6(was)-477.2(r)0.2(eported)-476.4(t)3.8(o)-472.5(p)-4.9(ro)4.9(mote)-473(macrophage)]TJ 0 -1.2055 TD 0.0442 Tc [(polarization)-494.9(toward)-492.1(M2)-491.3(phenoty)-5.1(p)3.2(e)-494.6(a)-2.2(nd)-492.1(PD-1)-497.3(de)]TJ /F12 1 Tf 22.3548 0 TD 0 Tc ()Tj /F11 1 Tf 0.5789 0 TD 0.0437 Tc (ciency)Tj -22.9337 -1.2114 TD 0 Tc [(en)20.1(h)11.8(a)0(n)17.2(c)0(e)20.4(d)-231.9(M)13.7(1)-231.2(p)12.7(o)0(l)16(a)13.3(ri)21.3(za)17.5(ti)18.9(on)-218.2(\()]TJ 0 0 0 0.7 k 10.8015 0 TD -0.0135 Tc (26)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc (,)Tj 0 0 0 0.7 k 0.4476 0 TD -0.0135 Tc (27)Tj 0 0 0 1 k 0.9369 0 TD 0 Tc (\).)Tj -11.8577 -1.2114 TD [(In)-337.4(recent)-337.9(years,)-344.9(many)-336(studies)-345.3(have)-336.2(indicated)-344.2(that)-337.7(helminths)]TJ -1.2651 -1.2114 TD [(induce)-346.6(PD-1)-346.6(pathway)-343.9(to)-349.8(modulate)-342.8(the)-350.3(host)-344(immune)-344.9(system)-351.4(to)]TJ T* 0.0188 Tc [(mi)4.3(ni)4.3(mize)-514.1(exce)5.1(ssiv)5.4(e)-520(i)4.3(n)]TJ /F12 1 Tf 9.5244 0 TD 0 Tc ()Tj /F11 1 Tf 0.5431 0 TD 0.0167 Tc [(a)-5.8(mmation)-522.4(against)-516.8(i)2.2(nvad)-6.4(ed)-519.6(parasites)]TJ -10.0674 -1.2114 TD 0 Tc [(facilitat)-10.9(ing)-501.5(worms)]TJ /F13 1 Tf 7.4476 0 TD (?)Tj /F11 1 Tf 0.7221 0 TD [(survival)-505.4(and)-507.1(promoting)-505.2(the)-505.5(chronic)-9.5(ity)-501.8(of)]TJ -8.1697 -1.2055 TD [(helminth)-492.6(infection)-495.2(\()]TJ 0 0 0 0.7 k 8.5039 0 TD (28)Tj 0 0 0 1 k 0.9548 0 TD (\).)Tj /F14 1 Tf 1.0563 0 TD [(Trichinella)-493.2(spiralis)]TJ /F11 1 Tf 7.5491 0 TD [(,)-492.2(a)-493.9(tissue-dwelling)]TJ -18.0641 -1.2114 TD [(intestinal)-212(nematode,)-212.3(is)-205.5(known)-212(to)-206.5(secrete)-212.3(molecules)-209.5(that)-212.3(modulate)]TJ T* [(the)-320.5(host)-326(immune)-327(system)-321.6(\()]TJ 0 0 0 0.7 k 10.6642 0 TD (29)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-322.2(Infection)-326.7(with)-318.7(this)-327.3(nematode,)-325.7(or)]TJ -11.625 -1.2114 TD [(treatment)-225.7(with)]TJ /F14 1 Tf 6.1168 0 TD (Trichinella)Tj /F11 1 Tf 4.2788 0 TD [(-derived)-230.8(proteins,)-226.9(has)-231.5(been)-221.7(extensively)]TJ -10.3957 -1.2114 TD [(investigated)-237.1(for)-229.5(the)-236.9(treatment)-231.7(of)-235.4(many)-234.6(hypersensitivity)-236.7(disorders)]TJ T* (\()Tj 0 0 0 0.7 k 0.3461 0 TD (7)Tj 0 0 0 1 k 0.4774 0 TD (,)Tj 0 0 0 0.7 k 0.6684 0 TD (30)Tj 0 0 0 1 k 0.9608 0 TD (,)Tj 0 0 0 0.7 k 0.6684 0 TD (31)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-453.5(Our)-453.8(previous)-459.1(study)-455.8(demonstrated)-455.8(that)-451(excretory/)]TJ -4.0819 -1.2055 TD 0.0191 Tc [(secretory)-519.5(p)-4(roduct)4.8(s)-524(f)-0.2(rom)]TJ /F14 1 Tf 11.0342 0 TD 0.0214 Tc [(T.)-513.5(spi)5(r)3.5(alis)]TJ /F11 1 Tf 4.8278 0 TD 0.0213 Tc [(ad)4.2(ult)-518.1(w)6(orms)-515.8(\()]TJ /F14 1 Tf 6.3436 0 TD 0.0157 Tc (Ts)Tj /F11 1 Tf 0.9608 0 TD 0.0212 Tc [(-AES)5.8(\))]TJ -23.1664 -1.2114 TD 0.049 Tc [(ameliorated)-547(D)2.2(SS-in)5.2(d)-3.9(uced)-546.9(coli)4.7(tis)-547.8(i)4.6(n)-549.8(m)1.7(ice)]TJ /F14 1 Tf 19.4188 0 TD 0.0523 Tc [(vi)6(a)]TJ /F11 1 Tf 1.8918 0 TD 0.0495 Tc [(inhi)5.1(biti)5.1(ng)]TJ -21.3105 -1.2114 TD 0 Tc (proin)Tj /F12 1 Tf 2.1842 0 TD ()Tj /F11 1 Tf 0.5371 0 TD [(ammatory)-312(cytokines)-312(\(IFN-)]TJ /F8 1 Tf 10.7836 0 TD (g)Tj /F11 1 Tf 0.4058 0 TD [(,)-313.1(IL-6,)-310.9(IL-17\))-315.7(\()]TJ 0 0 0 0.7 k 5.9319 0 TD (5)Tj 0 0 0 1 k 0.4834 0 TD [(\).)-310.3(It)-307.9(has)-315.1(been)]TJ -20.3258 -1.2114 TD [(reported)-387.5(that)-385.4(adoptive)-382.4(transfer)-388.2(of)-384.6(macrophages)-390.4(obtained)-385.1(from)]TJ T* 0.0198 Tc [(helminth-inf)-5.5(ected)-522.4(mice)-525(an)-6.1(d)-516.5(h)-4.2(elminth)-517.4(E)-3(S)-520.7(p)2.7(rotein-ac)-5.8(t)-0.5(ivate)-5.8(d)]TJ T* 0 Tc [(macrophages)-408.3(reduced)-402.6(allergic)-407.4(asthma)-405.2(and)-405.7(DSS-induced)-409.6(colitis)]TJ T* [(in)-398.5(mice)-405.5(\()]TJ 0 0 0 0.7 k 3.8551 0 TD (16)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-399.8(However,)-404.2(the)-404(signal)-405.3(pathway\(s\))-403.9(and)-399.7(mechanism)]TJ -4.8099 -1.2055 TD [(inv)-12.1(olv)-9.4(ed)-508.2(in)-511.9(th)-8.4(e)-503(M)0(2)-509.9(m)0(a)-10.2(c)0(r)-7.7(opha)-11.2(ge)-510.5(pol)-13.1(ariz)-14.9(at)-7(ion)-513.2(ind)-9.8(uce)-8.6(d)-506.4(b)-7.3(y)]TJ /F14 1 Tf 24.8314 0 TD (T.)Tj -24.8314 -1.2114 TD (spiralis)Tj /F11 1 Tf 3.1867 0 TD [(AES)-407.5(are)-406.2(still)-406.1(unknown.)-413(Here,)-410(we)-404.9(characterize)-410.9(the)-404(role)]TJ -3.1867 -1.2114 TD (of)Tj /F14 1 Tf 1.0622 0 TD [(T.)-270.1(spiralis)]TJ /F11 1 Tf 4.1416 0 TD [(AES)-270.2(in)-267.2(the)-272.8(M2)-271.1(macrophage)-271(polarization)-273.6(associated)]TJ -5.2038 -1.2114 TD [(with)-294.8(the)-302.6(therapeutic)-302.1(ef)]TJ /F12 1 Tf 9.047 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cacy)-296(of)-301.1(DSS-induced)-302.1(colitis)-297.7(in)-303(mice)-298.1(and)]TJ -9.5781 -1.2114 TD [(the)-326.5(involvement)-327.4(of)-330.9(PD-1)-322.8(in)-326.9(the)-326.5(activation)-330(of)-330.9(M2)-324.9(macrophages.)]TJ T* [(This)-224.2(study)-229(highlights)-226.4(the)-225(importance)-230(of)-223.5(PD-1)-227.3(as)-225.4(a)-225.4(checkpoint)-228(for)]TJ 0 -1.2055 TD [(AES-induced)-387.4(M2)-384.5(macrophage)-390.4(polarization)-387(associated)-388.2(with)-384.3(the)]TJ 0 -1.2114 TD [(protective)-390.5(ef)62.5(fects)-389.2(of)-384.6(AES)-383.6(on)-385.3(DSS-induced)-391.7(colitis.)-390(Our)]TJ /F12 1 Tf 22.4444 0 TD ()Tj /F11 1 Tf 0.5311 0 TD (ndings)Tj -22.9755 -1.2114 TD 0.0436 Tc [(provide)-543(n)-0.2(ew)-538.6(insi)5.2(ghts)-541.3(int)5.4(o)-542.5(the)-537(m)-3.7(ec)6.1(hani)5.2(sms)-541.3(o)0.5(f)-536.7(h)-4.3(e)6.1(l)1.2(mi)5.2(nth)]TJ T* 0.03 Tc [(immu)-5(nom)-5.4(o)-1.1(dulation)-533(o)-1.1(f)-532.4(t)3.8(he)-532.7(hos)-5.8(t)-527.3(immu)-5(ne)-526.7(s)-5.8(y)-1.3(stem)-536.5(and)-530.1(t)-2.2(he)]TJ T* 0 Tc [(pot)-8.8(e)-7.7(ntia)-11.6(l)-507.9(t)0(h)-8.4(e)0(r)-7.7(a)0(p)-9.8(eut)-9.2(ic)-511.6(e)-7.7(f)58.3(fec)-10.9(t)-503.6(o)-7.2(f)-508.7(nem)-9.4(at)-7(ode)-14.1(-de)-11(ri)-8.6(ved)-515.7(pro)-12.4(tein)-14.7(s)-507.3(o)0(n)]TJ T* (in)Tj /F12 1 Tf 0.7997 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammatory)-306(bowel)-300.7(diseases.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 122.0598 Tm [(MATERIALS)-301.3(AND)-301.7(METHODS)]TJ 0 -1.748 TD (Animals)Tj /F11 1 Tf 9.5 0 0 9.5 306.1417 89.5748 Tm [(Wild-type)-451.6(\(WT\))-447.3(and)-447.5(PD-1)-442.1(knockout)-450.2(mice)-447.3(\(KO)-448.1(mice\))-444.4(of)-450.3(the)]TJ 0 -1.2114 TD [(C57BL/6)-290.3(strain)-298.1(were)-293.3(purchased)-292.3(from)-294.7(Jackson)-296.8(Laboratory)-291.6(\(stock)]TJ T* [(no.)-388.1(021157,)-387.2(USA\).)-389.7(Female)-389.5(ICR)-384.2(mice)-387.6(aged)-389(6)]TJ /F13 1 Tf 18.1775 0 TD (?)Tj /F11 1 Tf 0.5132 0 TD [(8)-386.3(weeks)-389.1(and)-387.8(rats)]TJ ET q 45.354 114.066 m 289.134 114.066 l 289.134 66.557 l 45.354 66.557 l W n 0 0 0 rg 45.354 114.066 m 117.354 114.066 l 117.354 113.613 l 45.354 113.613 l 45.128 113.726 l 45.128 113.953 l f* Q BT /F15 1 Tf 7.4999 0 0 7.4999 45.3543 104.5417 Tm (Abbreviations:)Tj /F11 1 Tf 6.5613 0 TD [(IBD,)-435(in)]TJ /F12 1 Tf 3.0993 0 TD ()Tj /F11 1 Tf 0.5291 0 TD [(ammatory)-436.1(bowel)-438.7(disease;)-436.8(CloA,)-432.9(liposomal)-438.3(clodronate,)]TJ -10.1897 -1.2624 TD [(Clophosome)-249.9(-A;)-252.8(PD-1,)-250.8(programmed)-254.6(death)-250.7(1;)-247.9(WT,)-248.5(wild)-250.8(type;)-247.9(KO,)-251.7(knockout;)-258.1(DAI,)]TJ 0 -1.2699 TD [(disease)-269.3(activity)-274.3(index;)-268(MPO,)-271.9(myeloperoxidase;)-277.2(DSS,)-271.3(dextran)-270.4(sulfate)-269.8(sodium;)-275.6(AES,)]TJ T* [(excretory/secretory)-333.7(products)-326.4(from)]TJ /F14 1 Tf 14.0827 0 TD [(Trichinella)-328.5(spiralis)]TJ /F11 1 Tf 7.7103 0 TD [(adult)-329.4(worms;)-323(FVD,)]TJ /F12 1 Tf 8.111 0 TD ()Tj /F11 1 Tf 0.5291 0 TD (xable)Tj -30.4331 -1.2624 TD [(viability)-299.7(dye.)]TJ ET 0 0 0 0.7 k 45.354 737.518 504.567 0.28345 re f BT /F6 1 Tf 6.9999 0 0 6.9999 45.3543 744.2644 Tm [(Wang)-303.4(et)-300.5(al.)]TJ /F4 1 Tf 56.9126 0 TD [(Trichinella)-298.7(spiralis)]TJ /F6 1 Tf 7.6537 0 TD [(Attenuated)-302.9(Colitis)]TJ ET 45.354 42.803 504.567 0.22675 re f 45.354 42.803 504.567 0.22675 re f BT 6.9999 0 0 6.9999 45.3543 31.2945 Tm [(Frontiers)-306.1(in)-296.3(Immunology)-503.1(|)-502.8(www.frontiersin.org)]TJ 52.8468 0 TD [(October)-304.5(2020)-505.2(|)-494.7(Volume)-307.7(11)-499.6(|)-494.7(Article)-305.6(563784)]TJ -17.0811 0 TD (2)Tj ET endstreamendobj42 0 obj<>endobj43 0 obj<>endobj44 0 obj<>endobj45 0 obj<>endobj46 0 obj<>endobj47 0 obj<>endobj48 0 obj<>endobj49 0 obj<>/Border[0 0 0]/Type/Annot>>endobj50 0 obj<>/Border[0 0 0]/Type/Annot>>endobj51 0 obj<>/Border[0 0 0]/Type/Annot>>endobj52 0 obj<>/Border[0 0 0]/Type/Annot>>endobj53 0 obj<>/ProcSet[/PDF/Text]/ExtGState<>>>endobj54 0 obj<>stream /GS1 gs BT /F11 1 Tf 9.5 0 0 9.5 45.3543 710.4754 Tm 0 0 0 1 k 0 Tc 0 Tw [(were)-269.4(purchased)-274.4(from)-264.9(the)-272.8(Capital)-265.1(Medical)-271.3(University)-270.1(Laboratory)]TJ 0 -1.2114 TD [(Animal)-325.1(Services)-329.1(Center)-324.6(\(Beijing,)-329.2(China\).)-326.1(All)-328.8(animals)-324.5(were)-323.1(kept)]TJ T* [(in)-303(a)-297(pathogen-free)-308.3(environment.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 45.3543 664.951 Tm [(Preparation)-303.4(of)-302.4(Excretory/Secretory)-313.7(\(ES\))]TJ 0 -1.0394 TD [(Products)-304.2(From)-301.5(Adults)]TJ /F14 1 Tf 9.5 0 0 9.5 45.3543 640.9699 Tm [(T.)-323.8(spiralis)]TJ /F11 1 Tf 4.249 0 TD [(\(strain)-325.1(ISS)-324.4(533\))-326.6(was)-318.3(maintained)-331.7(in)-320.9(female)-326(ICR)-324.6(mice.)]TJ -4.249 -1.2114 TD 0.0247 Tc [(The)-520.1(m)1.2(usc)5.1(l)0.2(e)-520.1(l)0.2(arvae)-520.1(w)3.5(ere)-520.1(r)0.8(e)5.1(c)-0.9(ov)5.3(ere)5.1(d)-523.5(fro)5.5(m)-523.9(i)4.2(n)-1.2(f)5.4(ect)4.4(ed)-517.5(mic)5.1(e)-520.1(by)]TJ T* 0 Tc [(digestion)-496.7(of)-498(the)-493.6(carcasses)-503.9(in)-494(arti)]TJ /F12 1 Tf 13.8927 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(cial)-492.9(gastric)-496.2(juice)-501.2(\()]TJ 0 0 0 0.7 k 7.6565 0 TD (32)Tj 0 0 0 1 k 0.9608 0 TD [(\).)-495.3(The)]TJ -23.0411 -1.2114 TD [(recovered)-492.4(muscle)-498.3(larvae)-490.5(were)-490.2(used)-495.5(to)-487(infect)-495.3(rats)-490.4(orally)-492.1(with)]TJ T* 0.0218 Tc [(14,000)-519.7(larvae)-523(each.)-524.1(S)0.5(ix)-524.7(days)-521.3(af)]TJ 13.8808 0 TD 0.0209 Tc [(ter)-522.2(i)-5.5(nfec)-4.7(tion)-5(,)-525(e)1.3(ach)-522.3(r)-3(at)-524.5(was)]TJ -13.8808 -1.2055 TD 0.0102 Tc [(e)-3.5(u)-0.9(than)-3.8(iz)-3.5(ed,)-511.8(a)-0.4(n)-3.8(d)-514.1(the)-510.7(a)-0.4(dult)]TJ /F14 1 Tf 11.6429 0 TD 0.0112 Tc [(T.)-511.7(spiral)11.2(i)-10.9(s)]TJ /F11 1 Tf 4.7324 0 TD 0.0128 Tc [(worms)-506.4(w)3.5(ere)-508.1(c)5.1(oll)6.2(ect)4.5(ed)]TJ -16.3752 -1.2114 TD 0 Tc [(from)-342.5(intestine.)-348.5(The)-342.7(collected)-345.3(adult)-346.1(worms)-338.5(were)-347(washed)-343.2(several)]TJ T* [(times)-239(with)-235.1(sterile)-235.9(saline)-238.4(\(0.9%)-231.5(NaCl\))-236.6(and)-238.6(cultured)-236.8(in)-237.4(RPMI-1640)]TJ T* [(\()-9.1(T)-6.6(he)-13.8(r)-12(m)0(o)-520.1(F)0(i)-13.7(s)0(h)-18.1(e)-7.7(r,)-522(C)-6.4(a)0(r)-16.6(l)-6.6(sb)-13.2(a)-10.6(d)0(,)-521.2(U)0(S)-14.4(A)-11.2(\))-510.4(s)-12(up)-16.3(pl)-11.8(e)-7.7(m)0(e)-19.2(n)0(t)-10.4(e)-7.7(d)-518.4(w)0(i)-11.9(t)-8.3(h)-513.3(2)-10.3(00)-522(U)]TJ T* 0.0328 Tc [(penicillin/ml)-528.8(and)-527.3(200)]TJ /F8 1 Tf 10.2345 0 TD 0 Tc (m)Tj /F11 1 Tf 0.6027 0 TD 0.0313 Tc [(g)-537.1(s)1.4(treptomyc)-6.2(i)4.9(n)-6.6(/)1.2(ml)-536.3(\()4.3(C)-4.9(aisson)-531.7(labs,)]TJ -10.8373 -1.2114 TD 0 Tc [(Logan,)-460(USA\))-458.5(at)-454.5(3000)-453.2(worms/ml)-458.3(at)-460.5(37?C,)-454.8(5%)-453.9(CO)]TJ 7.1249 0 0 6.3326 243.4393 524.3527 Tm (2)Tj 9.5 0 0 9.5 246.8409 525.94 Tm [(,)-456.3(for)-456.3(48)-456.3(h.)]TJ -21.209 -1.2055 TD 0.0254 Tc [(Cultured)-528.8(medium)-523.2(containi)4.9(ng)-525.1(AES)-527.1(p)-3.6(roducts)-523.7(w)-1.8(as)-523.7(c)-6.2(o)0.2(llected)]TJ 0 -1.2114 TD 0 Tc [(and)-405.7(concentrated)-414.8(buf)63.8(fer-exchanged)-411.3(to)-409.4(PBS)-404.1(using)-411.2(a)-404.4(centrifugal)]TJ /F12 1 Tf T* ()Tj /F11 1 Tf 0.5311 0 TD [(lter)-500.1(\(Millipore)-499.4(Amicon)-501.9(Ultra-15,)-499.7(NMWL:)-502.2(3000,)-497.7(USA\),)-503(and)]TJ -0.5311 -1.2114 TD [(buf)63.8(fer-exchanged)-506.8(to)-499(PBS)-499.6(\()]TJ 0 0 0 0.7 k 11.1416 0 TD (32)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-501.2(Protein)-498.4(concentration)-503.3(in)-500(AES)]TJ -12.0964 -1.2114 TD 0.0546 Tc [(was)-554.1(d)-4.3(etermined)-553.3(u)-4.3(sing)-555.6(th)-5.2(e)-555.8(B)5(C)-5.5(A)-553.4(pr)-5.1(otein)-556.2(a)-3.7(ssay)-549.6(\()-2.2(Merck,)]TJ T* 0 Tc [(Darmstadt,)-307.1(Germany\).)]TJ /F1 1 Tf 11.9999 0 0 11.9999 45.3543 434.4377 Tm [(Development)-304.1(of)-302.4(a)-302(DSS-Induced)-304.1(Colitis)]TJ 0 -1.0394 TD [(Mouse)-300.1(Model)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 410.4566 Tm [(To)-455.5(develop)-458.8(a)-458.1(colitis)-458.8(mouse)-461.4(model,)-458.8(male)-460.1(C57BL/6)-457.4(mice)-459.2(were)]TJ 0 -1.2114 TD [(exposed)-263.2(to)-260.2(2.5%)-258.2(dextran)-264.1(sodium)-258.5(sulfate)-260.6(polymers)-266.6(\(DSS,)-256.6(36,000)]TJ /F13 1 Tf 25.1537 0 TD (?)Tj /F11 1 Tf -25.1537 -1.2114 TD [(50,000)-245.5(MW,)-244.5(MP)-241.9(Biomedicals,)-245.4(Solon,)-250.2(USA\))-243.6(in)-243.3(drinking)-243.1(water)-244.8(for)]TJ 0 -1.2055 TD [(7)-416.1(days.)-413.9(Meanwhile,)-423.6(each)-414(mouse)-413.6(was)-419.7(injected)-417.8(intraperitoneally)]TJ 0 -1.2114 TD [(with)-247.1(20)]TJ /F8 1 Tf 3.2225 0 TD (m)Tj /F11 1 Tf 0.5729 0 TD [(g)-246.2(AES)-246.4(in)-243.3(a)-249.3(total)-244(volume)-248.6(of)-247.4(100)-245.9(?l)-242.6(every)-251.2(day)-244(until)-251.5(day)-244(7,)]TJ -3.7954 -1.2114 TD [(when)-257.9(the)-260.8(mice)-262.3(were)-257.5(sacri)]TJ /F12 1 Tf 10.0734 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ced)-259.3(\()]TJ /F15 1 Tf 0 0 0 rg 1.9574 0 TD [(Figure)-259.9(1A)]TJ /F11 1 Tf 0 0 0 1 k 4.1595 0 TD [(\).)-262.5(The)-259.1(same)-262.6(volume)-254.6(of)]TJ -16.7214 -1.2114 TD [(PBS)-422(was)-419.7(administered)-421.5(to)-421.4(control)-421.2(mice.)-420.2(Animal)-420.5(body)-421(weights,)]TJ T* [(stool)-220.4(consistency)-220(\(diarrhea\),)-224.9(and)-220.7(presence)-223.1(of)-217.5(rectal)-225.9(bleeding)-219.6(were)]TJ T* [(monitored)-278.7(daily.)-279.9(All)-275.1(mice)-280.2(were)-275.4(sacri)]TJ /F12 1 Tf 14.5551 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ced)-277.2(on)-277.9(day)-273.9(7.)-275.7(Colons)-280.3(were)]TJ -15.0862 -1.2114 TD [(collected,)-264.5(and)-262.5(their)-263.4(length)-259.1(was)-258.6(measured)-268.7(from)-258.9(cecum)-266.6(to)-260.2(rectum.)]TJ 0 -1.2055 TD 0.0102 Tc [(The)-516.7(d)-0.9(i)-4.3(s)-1.8(e)-3.5(a)-0.4(s)-7.7(e)-510.7(a)-6.3(c)-3.5(ti)-4.3(v)-3.2(i)-4.3(ty)-516.5(i)-4.3(n)-3.8(de)-3.5(x)-512.4(\()-4.9(DA)-7(I\))-518.1(w)-5(a)-0.4(s)-515(s)-1.8(c)-3.5(o)-3(re)-3.5(d)-514.1(b)-3(as)-7.7(ed)-520.1(on)-511(t)-4.1(h)-1.9(e)]TJ 0 -1.2114 TD 0 Tc [(following)-343(parameters:)-350.9(stool)-345.8(consistency)-345.3(\(0)]TJ /F13 1 Tf 17.0794 0 TD (?)Tj /F11 1 Tf 0.5132 0 TD [(4\),)-344.5(presence)-348.4(of)-277.2(fecal)]TJ -17.5926 -1.2114 TD 0.0132 Tc [(bl)-5.3(oo)-6(d)-517.1(\()-1.9(0)]TJ /F13 1 Tf 3.7178 0 TD 0 Tc (?)Tj /F11 1 Tf 0.5311 0 TD 0.0165 Tc [(4\),)-517.4(a)5.9(nd)-513.8(per)4.5(c)-3.1(entage)-516.4(of)-516(body)-510.2(weight)-517(loss)-514.6(\(0)]TJ /F13 1 Tf 18.6967 0 TD 0 Tc (?)Tj /F11 1 Tf 0.5252 0 TD 0.0164 Tc [(4\))-517.8(as)]TJ -23.4708 -1.2114 TD 0 Tc [(previously)-306.1(described)-305.9(\()]TJ 0 0 0 0.7 k 8.8381 0 TD (5)Tj 0 0 0 1 k 0.4834 0 TD (\).)Tj -8.0563 -1.2114 TD [(To)-252.6(evaluate)-255.1(the)-248.9(involvement)-255.8(of)-253.3(macrophages)-259.1(in)-255.3(DSS-induced)]TJ -1.2651 -1.2114 TD 0.0323 Tc [(co)-4.8(litis,)-531.5(lipo)-4.8(somal)-529.3(c)-5.2(lodronate)-536.4(w)-0.8(as)-534.7(use)-5.2(d)-533.8(to)-529.9(selectiv)-5(ely)-536.1(a)-2.1(nd)]TJ 0 -1.2055 TD 0 Tc (ef)Tj /F12 1 Tf 0.6445 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ciently)-364.7(deplete)-370.6(macrophages)-366.6(from)-366.4(treated)-364.1(mice)-363.7(\()]TJ 0 0 0 0.7 k 19.9081 0 TD (33)Tj 0 0 0 1 k 0.9548 0 TD [(\).)-364(In)-367.3(this)]TJ -22.0386 -1.2114 TD [(experiment,)-226.2(each)-223(mouse)-222.7(was)-216.8(injected)-226.9(intraperitoneally)-226.9(with)-217.2(1)-219.2(m)0(g)]TJ T* 0.0191 Tc [(of)-513.4(clo)5.9(p)2(hosome)5.4(-A)-511.3(\(Clo)5.9(A\),)-514.8(a)2.6(n)-520(a)2.6(n)5.1(i)]TJ 14.3821 0 TD 0.0181 Tc [(onic)-514.8(lipo)4.9(somal)-519.6(c)4.4(lodronate)]TJ -14.3821 -1.2114 TD 0 Tc [(\(FormuMax,)-441.2(Sunnyvale,)-443.3(USA\),)-443.4(in)-440.3(a)-440.2(volume)-439.6(of)-438.3(150)-436.9(?l)-439.5(2)-440(days)]TJ T* [(prior)-301.5(to)-302(\(day)-300.8(-2\))-304(and)-298.3(4)-302.8(days)-303.7(after)-302.6(\(day)-300.8(4\))-299.9(DSS)-304.3(exposure.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 45.3543 157.9464 Tm [(Measurement)-308.1(of)-297.6(Myeloperoxidase)-309.5(Activity)]TJ /F11 1 Tf 9.5 0 0 9.5 45.3543 146.4377 Tm [(To)-306.3(measure)-305.3(the)-308.6(activity)-305.7(of)-301.1(myeloperoxidase)-317(\(MPO\),)-305.6(an)-305(enzyme)]TJ 0 -1.2055 TD [(pres)-12.9(ent)-507.4(nea)-8.4(rly)-503.5(e)-7.7(xclus)-11(ively)-509.3(in)-511.9(neutr)-11.3(ophi)-9.1(ls,)-504.8(an)-507.9(MPO)-511.4(assa)-9.3(y)-502.8(kit)]TJ 0 -1.2114 TD [(\(Nanjing)-363.7(Jiancheng)-362.8(Bio-engineering)-363.6(Institute,)-362.8(China\))-365(was)-360(used)]TJ T* [(according)-360.9(to)-361.7(the)-356.3(manufacturer)]TJ /F13 1 Tf 12.4724 0 TD (?)Tj /F11 1 Tf 0.2208 0 TD [(s)-358.1(instructions.)-365.2(Brie)]TJ /F12 1 Tf 7.6625 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(y,)-362.4(50)-354.9(mg)-359.2(of)]TJ -20.8868 -1.2114 TD [(colon)-394.9(tissue)-399.8(was)-395.9(homogenized)-400.8(by)-396.7(ultrasonication)-403.4(in)-392.5(500)]TJ /F8 1 Tf 23.6498 0 TD (m)Tj /F11 1 Tf 0.5729 0 TD 0.3945 Tc [(lo)394.5(f)]TJ -24.2227 -1.2114 TD 0 Tc [(0.9%)-288(NaCl.)-290(Then,)-293.8(MPO)-290.6(activity)-287.8(was)-294.4(measured)-292.6(in)-285.1(25)-289.2(?l)-290.3(of)-289.1(colon)]TJ T* [(tissue)-304.3(homogenate)-302.8(as)-303(U/g)-299.2(protein.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 708.6046 Tm [(Histological)-303.5(Analysis)]TJ /F11 1 Tf 9.5 0 0 9.5 306.1417 697.0959 Tm [(Colonic)-344.2(tissue)-340.1(proximal)-345.6(to)-343.8(the)-338.4(rectum)-344.8(was)-342.1(collected)-345.3(from)-342.5(each)]TJ T* [(mo)-12.8(us)-11.2(e)-509(a)-10.6(nd)]TJ /F12 1 Tf 5.168 0 TD ()Tj /F11 1 Tf 0.5371 0 TD 0.0106 Tc [(xe)10.6(d)-503.5(i)2.1(n)-498.7(4)10.6(%)-508.9(p)10.6(ar)10.6(afor)10.6(ma)10.6(ld)10.6(eh)10.6(yd)10.6(e)]TJ /F12 1 Tf 12.8663 0 TD 0 Tc ()Tj /F11 1 Tf 0.5371 0 TD 0.0077 Tc [(xa)7.7(tion)-501.6(s)7.7(o)-5.6(lu)7.7(tion)7.7(.)]TJ -19.1084 -1.2055 TD 0.0385 Tc [(Se)-5(cti)-5.8(o)1.4(ns)-540.4(w)-6.6(e)1(re)-542.1(st)-5.6(aine)-5(d)-539.5(w)-0.6(it)-5.6(h)-540.5(h)]TJ 13.3974 0 TD 0.0403 Tc [(ematoxylin)-534.7(and)-537.7(e)2.8(osin.)-541.4(T)-2.1(he)]TJ -13.3974 -1.2114 TD 0 Tc [(histological)-323.7(damage)-327.5(score)-321.1(was)-324.2(calculated)-326.8(using)-327.6(two)-323.2(parameters:)]TJ T* [(epithelial)-296.7(damage)-291.7(\(0)]TJ /F13 1 Tf 8.1339 0 TD (?)Tj /F11 1 Tf 0.5073 0 TD [(4\))-294(and)-292.3(in)]TJ /F12 1 Tf 3.7119 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ammatory)-294.1(cell)-291.2(in)]TJ /F12 1 Tf 6.8389 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ltration)-296.4(\(0)]TJ /F13 1 Tf 4.0759 0 TD (?)Tj /F11 1 Tf 0.5073 0 TD (4\))Tj -24.8374 -1.2114 TD [(as)-303(described)-299.9(previously)-306.1(\()]TJ 0 0 0 0.7 k 9.9421 0 TD (5)Tj 0 0 0 1 k 0.4774 0 TD (\).)Tj /F1 1 Tf 11.9999 0 0 11.9999 306.1417 617.1022 Tm [(Peritoneal)-305.4(Macrophages)]TJ /F11 1 Tf 9.5 0 0 9.5 306.1417 605.5936 Tm [(Peritoneal)-302.4(macrophages)-306.9(were)-299.2(isolated)-304.8(from)-300.7(C57BL/6)-302.3(male)-305(mice)]TJ 0 -1.2114 TD [(\(WT\))-256.3(and)-262.5(PD-1)-251.1(KO)-260(mice)-256.3(by)-259.4(washing)-258.9(the)-254.8(peritoneal)-260.9(cavity)-259(twice)]TJ 0 -1.2055 TD [(with)-318.7(5)-314.7(m)0(l)-316.5(Hank)]TJ /F13 1 Tf 6.4928 0 TD (?)Tj /F11 1 Tf 0.2148 0 TD [(s)-316.3(buf)57.8(fered)-320.4(salt)-318(solution)-319.7(\(HBSS)-320.1(without)-315.5(calcium)]TJ -6.7076 -1.2114 TD 0.0392 Tc [(and)-544.8(m)3.8(ag)-4.1(ne)-4.3(sium,)-536.5(G)-4.7(ibc)-4.3(o)2.1(,)-542.5(G)1.2(rand)-544.8(Island,)-542.5(U)4.3(S)-6(A)-1.9(\).)-536.5(H)-6.4(a)-1.2(rv)-4.1(este)-4.3(d)]TJ T* 0 Tc [(per)-12.9(ito)-12.2(ne)-9.8(al)-506.5(c)-7.7(e)0(l)-8.3(l)0(s)-507.9(w)-9.3(er)-7.7(e)-509(cul)-7.5(t)-8.3(ure)-12.9(d)-506.4(i)0(n)-511.9(6)0(-)-8.4(wel)-11.7(l)-507.9(tis)-10.9(su)-11.1(e)-503(c)-7.7(ult)-8.2(ur)-11.2(e)-509(pla)-10.4(te)-10.1(s)]TJ T* [(with)-312.7(2?10)]TJ 7.1249 0 0 6.3326 345.033 552.3589 Tm (6)Tj 9.5 0 0 9.5 351.4393 548.1069 Tm [(cells)-315.1(per)-317.2(well)-310.7(in)-314.9(RPMI-1640)-319(medium)-318.2(supplemented)]TJ -4.7682 -1.2114 TD [(with)-509.7(0.5%)-502.8(ina)-9.2(ctiv)-8.2(ated)-509.2(FBS,)-508.6(100)-502.5(U)-506.3(penici)-9.9(llin/)-12.1(ml)-501.5(and)-507.1(100)]TJ /F8 1 Tf 24.6285 0 TD (m)Tj /F11 1 Tf 0.5729 0 TD (g)Tj -25.2014 -1.2114 TD [(st)-8.3(re)-13.7(pt)-13.5(om)-6.9(y)-7.5(c)-7.7(in)-10.6(/m)-11.8(l)-6.6(;)-510.1(ce)-9.4(l)-6.6(l)-6.6(s)-507.3(w)-9.3(e)0(r)-7.7(e)-515(al)-11.2(lo)-7.9(we)-11(d)-512.4(t)0(o)-516.9(a)0(d)-9.8(h)0(e)-13.8(r)0(e)-515(f)-7.4(or)-514.5(4)-511.6(h)0(,)-516.2(a)0(n)-12.6(d)]TJ 0 -1.2055 TD [(nonadherent)-399.2(cells)-392.7(were)-388.8(removed.)-395.8(Adherent)-400.4(macrophages)-396.4(were)]TJ 0 -1.2114 TD [(collected)-303.5(directly)-302.2(for)]TJ /F12 1 Tf 8.5337 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ow)-297(cytometry)-304.5(or)-299.7(treated)-304.4(with)-300.8(AES)-300.1(\(4)]TJ /F8 1 Tf 15.2414 0 TD (m)Tj /F11 1 Tf 0.5729 0 TD (g/)Tj -24.8792 -1.2114 TD [(mL\))-229.6(for)-229.5(2)-225.2(h)-232.9(and)-226.7(then)-233(with)-229.2(either)-229.4(IL-4)-230.6(\(20)-226.7(ng/ml\))-228(or)-234.1(LPS)-229.3(\(100)-225.1(ng/)]TJ T* [(ml\))-277.9(\(PeproTech,)-280(Rocky)-280.1(Hill,)-279.1(NJ,)-278.6(USA\))-273.5(and)-280.4(10%)-279.2(inactivated)-276(FBS)]TJ T* [(for)-301.1(an)-299.1(additional)-305.5(6)-302.8(h)0(.)-301.3(Cells)-301.9(were)]TJ /F12 1 Tf 13.3079 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(nally)-301.9(collected)-303.5(for)-301.1(analysis.)]TJ -12.5738 -1.2114 TD 0.0421 Tc [(The)-538.5(R)-6.3(AW)-541.5(26)-4.1(4.7)-541.1(m)0.7(u)-4.8(r)0.3(ine)-544.5(m)0.7(a)-4.3(c)4.6(r)-5.7(o)5(p)-4.8(h)0.2(ages)-542.8(wer)-5.7(e)-538.5(obtained)]TJ -1.2651 -1.2114 TD 0 Tc [(from)-318.6(the)-314.5(Chinese)-313.1(National)-317.5(Infrastructure)-326.3(of)-313(Cell)-313.8(Line)-316.8(Resource)]TJ 0 -1.2055 TD [(\()-9.1(h)0(t)-8.4(t)-8.3(p:)-13.9(//)-12.4(c)-7.7(e)-7.7(l)-6.6(l)-6.6(r)0(e)-13.7(s)0(o)-13.2(u)0(r)-11.2(c)-7.7(e)-7.7(.)0(c)-10.5(n)-8(/c)-13.9(o)-7.3(n)-8(ta)-12.9(c)-7.7(t)0(.)-11.1(a)0(s)-10.6(p)-11.1(x,)-519.5(C)-6.4(h)0(i)-8.7(n)-8(a)-10.6(\))-510.4(an)-12.6(d)-512.4(c)-7.7(ul)-11.8(t)-8.3(u)0(r)-11.2(e)-7.7(d)-512.4(a)-10.6(n)-8(d)]TJ 0 -1.2114 TD 0.019 Tc [(analy)5.6(zed)-517.3(unde)5.3(r)-518.1(c)-0.6(o)5.8(n)-1(dit)4.7(i)-1.5(on)5(s)-518.1(i)4.5(de)5.3(nt)4.7(ical)-512.8(to)-513.4(tho)5.8(s)1.1(e)-519.8(o)5.8(f)-519.5(p)1.9(eri)4.5(t)-1.3(o)5.8(n)-1(eal)]TJ T* 0 Tc [(macrophage)-306.9(culturing.)]TJ /F1 1 Tf 11.9999 0 0 11.9999 306.1417 387.6093 Tm [(RNA)-299.1(Extraction)-307.5(and)-300.9(qRT-PCR)]TJ /F11 1 Tf 9.5 0 0 9.5 306.1417 376.1007 Tm [(Total)-319.9(RNA)-317.2(was)-318.3(extracted)-321.5(from)-318.6(macrophages)-324.8(by)-313.1(TRIzol)-322.5(reagent)]TJ T* [(and)-387.8(quanti)]TJ /F12 1 Tf 4.4578 0 TD ()Tj /F11 1 Tf 0.5311 0 TD [(ed)-388.8(by)-384.7(absorbance)-388.7(at)-382.9(260)-389.1(nm.)-386.4(A)-381.2(Fast)-388.1(King)-390.5(RT)-383.3(Kit)]TJ -4.989 -1.2055 TD [(\(TianGen,)-254.5(Beijing,)-248.5(China\))-251.6(was)-246.7(used)-250.8(to)-248.3(reverse-transcribe)-260.1(mRNA)]TJ 0 -1.2114 TD [(to)-367.7(cDNA.)-367.9(All)-364.6(qRT-PCR)-372.7(reactions)-368.5(were)-370.8(performed)-368.2(in)-368.7(triplicate)]TJ T* [(using)-267.9(the)-266.8(TransStart)-270.8(Top)-269.7(Green)-270.3(qPCR)-265.9(SuperMix)-270.4(kit)-267.9(\(TransGen,)]TJ T* 0.0339 Tc [(Be)-3.6(ijing,)-529.9(China\))-536.2(and)-538.2(Q)3.1(uan)-4(t)1.7(St)]TJ 12.9796 0 TD 0.0351 Tc [(udio-5)-530.2(\()-3.8(A)6(pplied)-531(B)3.4(iosystem)5.7(s,)]TJ -12.9796 -1.2114 TD 0.0085 Tc [(Ther)8.5(m)-9(o)-506(Fis)8.5(h)-9.6(er)-510.7(Scienti)]TJ /F12 1 Tf 9.5363 0 TD 0 Tc ()Tj /F11 1 Tf 0.5431 0 TD [(c)-7.7(,)-516(US)-14.4(A)-11.2(\))-9.1(.)-516(P)-10.9(ri)-14.5(m)-11.5(e)-7.7(r)-519.2(s)0(e)-13.7(q)-9.2(