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Toll-like receptor による自己免疫・アレルギー制御
*47ÛnÅb;_^Ccs — ¦!)·É³ÊbZcAc+ÎÑ9Ë% — õw Ý ÍÐð nÅS<@bvÝ¢ÕÍÐæ òi Ü ,1* nÅÔ+ñà)u+d$,â/&2)®È+x~')7Çxj+ko9Ì 89¡ ö7'*7Toll-like receptorúTLRû,?aONBGa)(+Çxj*pë)±q9 ãç®ôy9ä7_JXKc&7éTLR ,Çxj)(+Ľ9ãç7" &)»È)(*4#%Â7Û+q*7Ò*2óe%7'{8%7 5*ÛnÅÆ+Ç* TLR +GEP^¹óe%7'2q#%%7«æº& ,ÛnÅb;_^Cc+Ç*7 TLR ' +óîq+µÚ9°å¦!)·É³ÊbZc Ac+ÎÑ9Ë!©é+Ìá*$%2ê.%0! Û¼nÅ'ÀnÅ nÅÔ,g*]aTÁ¸è7ÀnÅÔ'ZD`V:cH3´¿ÖÙ¸è7Û¼nÅÔ'* q87ÀnÅÔ, B ÖÙ5ÃÂ87nÅE`W]aú=jû3 T ÖÙzj*4 6¾ÄÊ*Ľ9ãç7j+ñà)¾,²)x*7²9ª7+0&) )?V>DKcµÚ*27nÅÒ*%©r*ÃÂ87j, IgM &7nÅ Ò+ïß''2* IgG 3 IgAIgE D\I+jÃÂ87+µ±,D\II<ML×£' |-8T ÖÙ5ÃÂ87 IL-4 3 IL-5 )(+F<NA<a3 CD40 )(*47ÖÙ¶GEP ^)(*4#%s87 d§Û¼nÅÔ,UN3Z=I"&)]aTÁ9!)R?)(+¨Þ5*¯½) (Ó)Ï*l8%7½+Â*÷+®ôµ±&7Û¼nÅÔ+u,®ô +©tØ&ko!Çxj9ì3*ãç¡ö7'*7 +!1*j+4)¾Ä Ê)Çxjãçµ±,!Çxj*pë+±í9ãç%Çxj9 ù¥¤¡ö7Û ¼nÅÔ*%Çxj+ãç*fÊ)u9!%7+TLR &7 Çxj+ãç*7 To ll- li ke r ec ep tor TLR ,m¬R?+ Toll +}hø+Y[`E'%D`cQaE8!2+&7Toll ,R?* 3 ÁÐ/ÖØ,YCND]+Toll ¤I5!Ñ"ÁÐ/å %Toll TLR "' ÈÌám Z3@[!Ê+Ý¡ß/}!ÎÙÞ}D[J: +£Í(¡ßëe, *' TLR ,²Õ,TLR "` %^¿ÈÌ(l¿ÈÌ ¥0 ),ºrfÖØÄ/ÚãÔ壡 R:ZL1]A¢®ÈÌ( B ÈÌ!j¸ÈÌ '½±Ö&*-, *TLR !½±"j¸ÈÌ ½±, æ- ,." TLR ÖØ,W7[H"TLR !Äë ))§%,h# TLR4 ";VT çÐ!¡m+Ò»!r|, LPSì5[HG8@[í/ÖØ,TLR2 ";VT èÐ!WQPNEH/TLR9 "ÈÐ! CpG-DNA /ÖØ,b^!)É"x TLR /¤ R4BxW7[H kt *m ,TLR f!ÖØ"Æq"h# TLR4 , MD-2 ),ºr "À LPS "ÉyTLR4 !ÈÌám LPS "ÀÉy,. MD-2 " LPS Éy,o/TLR4 "ÈÌl /d,o/) cy iw om,Ë*-,% TLR2 " TLR1 ( TLR6 cy TLR WQPNEH/ÖØ,Ë*-,!) ),·¬!ÖØ"TLR q¯" Ó!m *,Ó飡, Tol l -li ke recep tor ),2YX9]\Ïj¸n— â/ÖØ, TL R — IgE "}2YX9]t ÃÈÌ ãÔj¸;ZMW[,2YX=[¢®ÈÌ!r u+Û%-2YX=[/ÖØ,OXJ]TìTh2íÈÌmp¦2YX=[ ·!, B ÈÌ IL-4 !?3G63[gµ, ) IgE f´³-,Ü !ÂÅ *TLR9 W7[H, CpG-DNA ¢®ÈÌ%"À B ÈÌ gµIgE !´³/ n,* -" TLR /a,Ï«j¸Ç!iw°j¸Ç/n, /Ã,TLR !iw/n,2YX9]!¨¼ µ,'Ã{ , ÜTLR !·¬"ª» m/ÖØ,Ã{-,TLR ,ºrf¶m!>[DS/ )àê,K2XZ[â!Ï! ),Ïr!ÖØ ä"TLR !W7[H+ Ë-#*>[DS"×<]B '~z-,ºrf! RNA ( DNA /ÖØ, TLR7 ( TLR9 Ï! RNA ( DNA /ÖØ ,vÍ,* :VB!Ïf!´³ â!ÖØ KG! SLE !UFXR4B/µÂÅ *º¾ IgG2a IgG2b "TLR9 !iwãÔ,Ã-,-*! * ä., TLR Ï! âm!ÖØs$Ïj¸¹!º {-, 4 ©ä_,à ¡HttR(§©% TLR gMSl RP105´CD180µ TLR4 Z B LPS §©=m±'%Rd%# TLR2 U¨¡9543.0§© ±'%#TLR7/9 $~® ¡¡HttR(§©% TLR 1)79>Rd%RP105 bR MD-2 ²FRd% MD-1 EY% RP105 x6*-¢BM,;29< IgG3 IgG2a L G@%#u RP105 vH±A% gvH" rª&% gMo%±¬(¦SLE 8/:6*-´MRL/lpr-lpr 6* -µ RP105 x(fN%¯`6*-«¢! Dy\ k#& ´^ 1µ}#RP105 KW HP¢ap! SLE s±A % Cq&~®(§©% TLR ¡ttR(§©% TLR gtR(§©%Vn %([% u RP105 EYRd% MD-1 h6*-¢BVnse_%({ ## SLE 8/:6*-h6*-«¢ MD-1 ° c6*-T ³OaT%(¤Q´^ 2µ #T³ SLE 8/:6*-X] MD-1 mRNA ?z §&Vn MD-1 =MhsI#(w% (i$_ MD-1 x SLE 8/:6*-(J£B%MD-2 $ MD-1 LPS Y9+<0{#9+<0({#%o s% ¥{&% |j&% '$ 5 TLR $'¼¿¨*ÂJa('Ê»uÌq'@~ TLR UI*¼¿' %$¶jvN*"¼¿k$ &¶jLt®'"N% TLR kË«;-93Qµ¢R ²ËÅ"¤[('OÄ TLR4 HWN` MD-2 ÐY´³É':;03= É"W'¤('$TLR tË)&§t %l&*!'TLR 8+:;?N`#ËÅN`st>Lk> Qs9?.?&'*¯Ep"%\£¡ª5?1*·©P¸>S À¯' ¾Ã ¡ª*ǹ'&odͽm*{zÏ'eh TYÈi ÒÓ eh ¸ ÅWHwg(' 11 ¥G ÒÒÓ¬] ÒÓnÁ]2,6ÒÓ 4,.º ¸ÒÓ C¸ZÒÓSiÒÓe^Rbi ÒÓÒÓe^¸Z¸ZÒÓÒÓ ÎÆ];?7/:.<ÒÓÓu¾ qxfÏ ª°'D_bS¦b¡ªwAcKF|y"u¾B ѱr|yMX¡ V¯} 1. Nagai, Y., Shimazu, R., Ogata, H., et al. Blood 2002; 99: 1699. 2. Nagai, Y., Akashi, S., Nagafuku, et al. Nat. Immunol. 2002; 3: 667. 3. Nagai, Y., Kobayashi, T., Motoi, Y., et al. J. Immunol. 2005; 174: 7043. 4. Kobayashi, T., Takahashi, K., Nagai Y., et al. Int. Immunol. 2008; 20: 881. 6 ] W p @ '3)/ E-mail: [email protected] [n690303'3q3cg'3 ^%qHlcgx< 5-"JG 3W :A 7 ; 3 O z'e03'3'3e (T :A 10 ; 4 O z'e0303'3kcge )/uf 3 ^rY3PQ 1JG :A 14 ; 3 O , nW :A 7 ; 4 O z'e03'38_ !e c' :A 8 ; 4 O zbh_2\ !e c' :A 9 ; 4 O \._ !e 7' :A 14 ; 4 O e3EsFoVU B]a%|cgI}T )/cg R03'e3cgC ?S^ ?S~3# C8 4JG :A 16 ; 3 O Oklahoma Medical Research Foundation, Immunobiology and Cancer Research Program, Associate Research ScientistPaul W. Kincade )/ :A 17 ; 7 O , Senior Research Scientist M :A 18 ; 3 O R03'e3cgC ?S^ ^vj# &D Xm>JG :A 19 ; 4 O 690303'3q3cg'35-"JG C83LQ^3LQ!e3 cg#^3TLR _*tyVUZ`^$=VU +{i:A 14 ; z'e0303'3kcgedwK{Nd{ 7 14 Young Investigator’s Award 8