ࡱ>    /1 !"#$%&'()*+,-.02Root Entry@DocInfoQPrvTextScriptsr0r0  !"#$%&'()*+,-./0134789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[]^_`abcdfghjklmnopVjA=U}:#iA7fVFMA:&N\pq 0K U]=VwS5AEMns֣*FW!5 F*k2g)N'aIPtB\szȷZZtx؂]oQ_~hO3违nV1%$h}`‹9p̓)Lz2 W{2 ̨?l-07o K(f{Qž,e=9Qyemoy풿kQ?7+P v1?\DE N̝Z"g!VmD 3(6Vi ?Xtvobv_oowμy`% %G&<1 Ն+j=8A 7A 8cD;b$c'IHةv 2Fr1v:|I`g gd b?* (s-fu"&@([[ΪZ)̀nx8S߫{ FhL:˵nӪ>{-WeQ 8HOuȾΗ-VbVW]ٲ̰!S4Zxak=7x:û\Wz/ŏiyFKv瀺4cͺ',D~l2N\ɇ8~lG̎S-˩6zsh0Ol~vxi_^Wd/JP vK*Arv^5R*rժ}7+;{}o78] <\><Chitinase-3-like-1 is a novel target for enhancing Th1 and CTL responses to inhibit pulmonary metastasis> <\Դ><Chitinase-3-like-1 (Chi3l1) isknown to play a significant role in the pathogenesis of Type 2 inflammation andcancer. However, the function of Chi3l1 in T cell and its clinical implicationsare largely unknown. Here we firstly show that Chi3l1 expression was increasedin activated T cells, especially in Th2 cells. In addition, Chi3l1-deficient Tcells are hyper-responsive to TcR stimulation and are prone to differentiatinginto Th1 cells. Chi3l1-deficient Th1 cells show increased expression ofanti-tumor immunity genes and decreased Th1 negative regulators. We generatedmice with deletion of Chi3l1 in T cells show reduced melanoma lung metastasis whichhave increased IFN and TNF-producing T cells in the lung. Furthermore, silencingof Chi3l1 expression in the lung by utilizing peptide-siRNA complex(dNP2-siChi3l1) efficiently inhibit lung metastasis with enhanced Th1 and CTLresponses. Coll>u@DO 6C,H,#GB!k0~ 6*7=M*Z:ҙ#?*?ӿT@Y~X+mj3'm[v|:j)%C$Mϼ5#cd߈W=lU[g BK,(Hl#'qNBPo׾Un;S]AHJ@H0 )ˈй3{o˥Nv޼ofyu'a,עoDefaultJScript2JScriptVersion5 BodyText r0r0Section06U o/j܏?|WtBzyg6Z;ɯm<4?"Z)ww,[4 a>Hy^Ol=fj}²A/3(̵\pȒ49$ 1.UxDqr>Ni:L:]^}*lf$ؙx-3VOX}ş|KI,\0g2uB,1h|$j&Xʁ$ ܵF$d~Ut b oOP+*T:_:ž}F^zBhNnky#@#}ES@mMR|3a2{LSFL-(٘ 55tL` 3!T!fȊ-^|Iׅț IpZwG YDh!c;:*2GӇAug+qVq0H:#۰#l-Puݡ n&WuT*]!h62ɽ*4*dZe7d3;%w1k Z1:k'`>1w03%ٰ鷎>7ٳұKf´KmFHWs:/*:Wy~X~R3βs}:ėOhPI5^h [(t17'8jVaax^DAÄ!&󎢗<^$MҴ֙_^^/D1.F7\ Xufum~θܦ?Bd n38%$k~J-q!͐гlE ;A֧Q\scHfdHecH:  @^%LCt&CP*2404 /!8#JdH6C ٠_G)PbbpYtE C N7밻T!.:JHI_ vfӡ@>t6~:BM!8] <\><Chitinase-3-like-1 is a novel target for enhancing Th1 and CTL responses to inhibit pulmonary metastasis> PrvImage:DocOptions r0r0_LinkDoc\ FileHeader ePNG  IHDRjsRGB:fIDATxY}IU?8< *t - 1јHB|51DcYfFAPp@P@Y^9߽UɽwժUU[>t6ÍXq eE-0!o!īQ!CVCW߅C  GX} !^} !2B.B%9>Z<|DcՂ_N7kte}֜U||++;/|;5OO('~'Nַu[>__|}ޔMozɟTHK;3X0T??Ӓ"7=KS͏Nl\9G]wz_گM˛~ww*6A'?uNd>=>^`#qQ'~'6~7x3 :Ug${!(oy[&?c5OBhĦ鬿˿o|W敯|xq> |9|?LЯ}kdQT}@E/zxŴ?dֶKd׽nD4>4M84__8\(DuRB.1 X OSߟ:(/ocM+ݻ#?)om>>mblRM +͇~J Klѝ*x0 ~NQZu"#@K yϚ忔Q=:K_ޗ9=Zaj[-_>O|I[ۤ>_Ȍ(#za #JҰmx3"yE4կkA-MK;dzG+W/M|*mm\iZ>z?3җt?|鋄 UWYMSo2xHyFZ(B u]wLSuoy׻5vm9ֳQľ nG &@ٻaʷC?'яq73ȇ!N"ĀO`bsY?~[[PKAԄ`8hOЁK.t o90cÑq__┚vtg?Z(PqFK*EF:YѲu5ܲ檐h}0Y&~Z£ҧʳɩ<&n.<rZkK[KHm :,hdGONNZo̓57{tx[Y4j^WM\Q{)H_ SǚF!X&po-7~7xq5-J[.Yk_8zTF* XџdeAG~GNòt8* #Z FEjhA=o.Bb#tFSAqju◼B k~)< Sx8TtbGiuQ`4myXt9}5~}5jky|+Gn.l;ZfK6,y-"5]}m+ͷǷ 08fyW}y *ԉXt%nNQ<.<].lK4^[hk>s*!C+&cC:-?E;2dFjaΓiy0,џpHo薞32Amvp1 Ox´ niיI xVD\H]@lһmLp9xJ5m??< ӟ)r~j-gkveQ޼/~t[ LȾq :@2UGeVvyog~!&# NRIb8GWU tuיz[' d>u*5@ *xJzyV!VfHYQϴOQܵ OE5*] |\EXl>7͕kھJCQra&':Dzԛٱճ󲽐׳nەὰ] kC-_y&q_xーiC?.~[\ү?%w:h8ZDHowK^wq//LHZ fsL:.[9⢓sDI hы'cfgC7?V]@]=D@ ,bzҚz+h, "ֹys{7YT1%or.OJ-5&󀢯Κ!+*-P:o-bh^~xD\:3<+@L>~>KG UGͧSvЉTU#dv\xhGxC?BK# 3']iZѵ 0:*ayC.~ Ft2sd@BON㻾뻦cm-Uݛ*5VFo Z91׺T~kYc/Ս*piT 6Pʟ72SP-TezH+rRʣ.GN<5FBojoꁸ1MuO?hqz&`zGP{^wC@O/42!];kv9^/@_٤Soo6z6s샬7cV?Lnu8BǨ.vщP[=P|j;u&.szrpʰ)\5*$yH$>;ofZ&qQķ~OM9Zڹ}+y޴_jHW*sv[]YB?a׿oɷg/aYKstKx_&*`xc:E}z%]Ttl$  ~3u _4'k0jJ H~(shZk ^n7| /omdե*->tu,rMͰCXuAuذ:im1cJ\!S z گNyZx4,[9 `V7I2MXF>r # k]o| ܻ/iO@Nɭa=AK➮+ڇ!GiO׬49y 37/);VJX]C9&}4#a7ꟷ7yӟGΛ9]ظS\u̥z77#tK_mi۸cM:GA5O2@ UKL?Unˬ%z,D -=3´V:j)?R&NVRщUv;j  )}\-o)?+ ?0lA׮.ofvFg4F@Mv{U܌50xr_׀:@jFX}{a҉#ʤ< VK?)̇mLՑK㝯???+6:ok;v|Tj/۳1 ^_A@_jx);~4m^㶲qKKX?KKmwUT*ݶx*]hSmm\^;u#vwv45b0z4-}.aɧ?G3|vŇRz<3/MT*肎S)0Fhu[lp1,|~ۿ'Rn0`7jj;yul'=u[Bӵ߷V.[ :Y>(erI2޶w;@;-ѭ>Spe|G"$Ook#NG!oǼXV!KfX:mu BV5U蕭Z]C &|Du륕[Vp  ` ]p>%ɰո`9@,HLe<).@+`xI *vNj:kiHѦn#a[ë'am oJ%,]<·{Lxx{.<<';%(uYSQh X#1DODgG/3z(oci9tK枵|@j-NJfgϖCwthFU4ΈZ}?Fԣ//tTA ~M.i:~%)!Fy7( =Q,EQDg4=4ξ';nL5ucf1+0@@al͇AߌGtrSL?UFuTvc'>*z/'g,F|,G5Siv)V 7ZB Th:pK~Q4UV_gdz"蘞Z~{.з\Z: > <<5,}ӕ&vubhnΫUW};kx좻/Oseꞷ9ښwK_xU-?Nҥ݊O⦲³<ͯ8 ӹ(=]]GKϭm3XCoIcP:`]S7tJtIe+V.G e.5<+xͻ'0ЅSNږ. eGl—A~.N1zJ.q!>$FC03񌉬0 0"P>:ǃ( O =#Ai惋`AϥUy#N^ЪExR:g# Vh_4VT雾i FIs-B@n~Yճ 2NE8 Q [bm3vLZkPq5}^<->4ʔ89/|"N%ੳֱ,氨yy=^ݯLėr'Ot_ܩUFzݗVF d* E]8&PjKQYg|@-o",)]*-O|5v\??>s6|-5.'LVFlT#40T:V'$pDY )]Dz0N+@tƕKyxesWЕ W.|Z =0Vh+u몴>:m}bC{*n5.Szz\V^}斳Fʞym*r𕷖9i׶`,RfP }we-vQ>;ߢm'<+IXQ˒t~& ℇGꇾ7uIX xq- 3:bF1FS<- lYK1Pc y=tKc8?lPB'ċ@9nzvzjc >VmE~­2vPI~oS49w=6Ԙo4 b=}YYu[mh.>+}(򾑝jxJ]3UV!A#G/Yt26Cm8#6)ٻk(F#!Kt1=ϞcX~xnӓqÕPbi?!fC+NY8;ޔnTm0[}TLG%S`wzd!QC>uŝ V5 ʳ&<ͮ_<* vg4m>%lG¼ǟK|>u>Ye40R,qmʳvUmݻKZӵaQ1jA\Og֒υWf=\sxʯg m手9v ϫ.j@0E/8zS=GV{ԄcC 0Wn7kǹkkuT#ukyѕCcփUFf`7b&; xnb /\h,N~@X8 .OwKMzֳ&Pl󑏋I]Yj]aϭqvJnB0PlN.{Զ@3kAYR`ǎ4@ P3OV,ą'!T+fטhꐟDh#,B5J]Ǻ|L>jԗV)>>Υ> 'M/LJе.>k'=MZx΅J+>9d*vR 0tU:+б%@4-[?S@Nz d~K_:OТl Q6=߳yS|WKgy)#;,gѰXX:e{g b3N]AE[k$Ityzst}ڕumF/CFV4 a2t.sgX^~H(A!6[CHpu|@G,ġ]|p~Ӟ6XʘW l2_@#c!/zыKP(8 ,6|X*]Vg5ZK뽗^s/ ßK ĵjVK}d)m>'aw%iiװ4`1nsm>=9^}:F8Ff\ 8<#]姜/".e{9*<[|C}_nVXaL8S0ef9X n70Hc7d`IbgDx`KNW? 4l<+Xj+%/y;  #8CEEzGB0kOi_TS7<G[HLp8/ NX9`cn&y',̪ ` /yʧ#| )0 /4V>2[<`NʒOtFQ+ 73!t).Vnu2M}aGVjfOȿU%m8z<ϥY:Z݄EϬ-#7ť yoiWX/>{~Zʻ>MQ;I`:vΊKOXYݒ]X>|Rkz~s8IӋu 9jxƯ4~^: ˔IpLХZװ6fSFL6XF_nءeZo5ʓNj:%Tk UV^֮:3w3Kǀai]Zz_t7GάVj>vRsD\U7[.:U1$;uQJ#d]YGR#fǙtDy2yBKxh h۝w~ M~"$>2!஝9J촥#R^6v´/~V̚)ī++>tՏ ە [«as˿}K]} 6öOeϓf|-e|,Ku d\@k5ՉU &h!7A'^* !pMЉW CB|tU.7ANb/MfGMЮ l$ ̫N: !>`DYEmlq랜|vhrgn"YXmU;;Bl;~2%-ŷy\X7,uN ̝jq{«mwE<65ٴ8^\t iD^'pN9a܍.Csw_w?;냩y-@Ev15we2CKkqA4T#_Wo뮩<| Ç#Q^ R+co98wos\޶5k.^qȿoҠS.~QvW;VSKk2j3qnq5;:` 0}htXH&$O~;F={{$vJ<==GA>u"86^ \0^}A%*)йE){f$4NiNq#nTܠrS O8;r7C o}t-6{xY2t7:K<QW=i6 m]X.*W'tDw:Poo=^n ]׼',ʪ*&<p/|IXҢQtb.5mZg^vLrQ[<:ҙZ3݋GU~<\-9omoԙͅΌaV:'Æ6eHxЬ?WkĜ v>? 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HoweverHWP Document File`a``a`0x  \ h tajou2010D 2 10| ”| $ 2:36:28Jemin!9.30.1.1558 MAC64LEDarwin_17.4.0@m @p-@HwpSummaryInformation.i