Title
The absence of indoleamine 2, 3-dioxygenase upregulates type I
interferon production resulting in suppression of viral replication
in retrovirus-infected mouse( 内容の要旨(Summary) )
Author(s)
星, 雅人
Report No.(Doctoral
Degree)
博士(医学) 甲第835号
Issue Date
2010-09-30
Type
博士論文
Version
none
URL
http://hdl.handle.net/20.500.12099/36544
※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。
Lt:/(J(;i=ilt..I)
・1+(_;Ia) f_.rL:rL'i
*JiEti.-b--S
-P,-I;i-/=[LI:1.1.ij. n (.)-I:;I:(itu -Lj-lIll-II
--I:;:i(:.J!:"1l:iT-i-)iEi-[;1
I.i:,:1tl:.-i< rl
[
6]
3i # A (--ry-Ht.[ilL1.T{) 1tli-J= (Bi'BS) q7Hi- 835 % -TLfj3t22 iF 9 A 30 P I:;.'=[_1J!-.)ilulL:TL-i,'t:Ti-1 1TL.;-.iiL']
The absence of indoleamine 2, 3-dioxygenase upregulates type I
interferon production resulting in suppression of viral replication lLn retrovirus-infected mouse
(:L]tE_)
_f*J-.i[r:.iLL tJl.)u (i.,ir):.tL5)
,.Ykli.-it':lu,I,./A T:_,'i',_ ,j:kJl rfl I:..,- ik
;GXFq*0)fEi
L, T,t3 (7
JI)L 7U,.i:Hii5.JE!=tti)i)[5 ,tQI i= ;!L8 ft?if7T=/i=!lLiU)l1.']))rlEtt,llLl(lil_1i:,y(Tt
'u
-)I.:)tdU)rr".]3JiuLJtLI i)-?-?Lt.) i), i a)jt?iSr,i:f.1'iU))W-t]jHit.jBLt!)TITL:iF-Tt{7.-D>3l ;EiF-, .LytZii7',∼"/ r1--L'!Tt(Jt-,',T37- 1)7t I,
7 7 >l
li;fme)*ig##-e>ba/ > T<.-/L,7 -I>B*#,I;.lihn## (IDO) Ej:, 4!FjEJr&9-/ h*/ >rCh#*5n, iE!!Uitft.1ifTl;-ufi-i)LJ(I-i:-LL. L Tut Elcii.;fL-i.i. >3., l[)0.'i]JClt'.i:i.TIT)JB413ftrLl',,a) 9 J{)L 7, fi!Hil.i5.)'f_:=J3LIT-,' Jt/
r3 7 7.
-I)tJJJt.iJJ:rB-I.1)i.it.P7lJbTt3ETllTr73 /J1;,
.:.TiiLI1;1,'fiiL'L-JHi-:I:-/iT7)1fJ/JIT..'i,iJ.1i
':.
A=#f*nSj:, 79R L, T,t= 9/}L,A-e>ba LP-BM5 9//I,Rk, IDOiaLZij19(B79Rb'iUHDO PR
I;i-.:-i7.7ii!xLS-I f) A i.=J,Li!Mt
Lj:-ti-,Il)0 ;I.i a ft?if''t)1)fll)r^kflViU)I.'J7II-fy],=y.:;titL7fj=,
[#&t *;'L]
4 iq#e) C57BL/6j W4=#iq7 9x (WT), IDO i&lfi+9(3A79R (IDO-KO) jb'ctU<1DO PRf#32ji-?
9R (1-MT) 8= LP-BM5 91}L,RkBkBfPq]2SL,f=. LP-BM5 9JI}t,RBB%i&, WT 79R8=hlV'rC,
Jt']1/1tit):-LIJT, I)7- 7,7 -r > fti:!]1Jii15A,Ji-f.Jsii!tltf.T/:[t='} t= 7, I, I/=/ 7
I(-I.(r'J'I!f)I-L , h.l[T!i:;I)I.Il-h[':k-LTtU)II)(I)mTlh-..1
kE%B9 RT-PCR.I2iT^, IDO i E) 0)#ga%is
ctUi+#fR#B]B&k, western blotting ibjS'itJi>1h#,iR#4g
*Thn#X=3E%& (rnIDO, rn CDllc 3fcI4=)8=T#-#hL,flo W=, IDO-KO klU<1-MT A,60)B*EB*
・lff,1TFllL. WT _La)-:ffliJti.L'I:.SJ.iU:q[h'f.-tHJi+TIT,-J}/ i.. V) mRh-..1 _L !yi ,, y _.L.'L:a)i-i:tf.:1'i-'Ji:il'([]n(T-t'Ct( Lt
331U( ELISA i2f-eh,raF$8=,*mB6]Ei#*k Flow cytometry i3f8=ct 9i;bW9eLf=. 5 68=, LP-BM5 9-Ill,
R2iS%i& 8 iBT.0)B*AB5* LP-BM5 T> / /I,A = tto-&kjEJt%Bb RT-PCR i2;ThASW L,, IDO-KO 75,6 nB*#P
B5Ji 9 CDllc F&Jr*#PB&k*B#L,, ex v1'VO -elype I IFN **DrnI4=tt%3S L, 9-1)VRtB#n$lJ/jilaBt k#ujEJt,LT=o 4=Hj1*0)tbW9etj:, Toxoplasma gond1'1' i LP-BM5 D=3EB%%j:1'}L,b8V'Ej:, LP-BM5
iiib'4.A.i!F.Jt-;a-7-tt,L,Ji-nil'kL tB fJ!J,t'.'i,2 ill(:[["'ju,ltLI,1*.'ii 4*'/t'&,3 n'itL"lll).Lu)LtrI.::2;I.I+i-jf: i)7tlJ{
;}r)T--ch*&jE,+L,f=. 4iTT1-*0)tbW9eSj:,Kaplan-Meier iiiLog rank A.5&8=T4*E L,f=. p<0. 05 ntB%k#=+
t'T'J-(1']LT.--,i;-:,i-,)i)
_L}:Pj7ii'L i'=
[#=5E]
G) LP-BM5 91)I,R2iB%i& WT 8=b'V,I, A.I#* L-*5< i,=yEj:EgS%i& 8i@rehjeB%-7 97 i tE#T9e
LT#%8=tebD LTi3 D , rE)F$8=T, U 7o L 7 7 yEj:#%8=1itfLTVlf=. 3:f=, B*BRi* IDOmRNA,
]I)0r5.YJ.:ill:-ti-,l.JrI!J,.J:U;1[)0 JJ i, - I/
_.L.Jt:Ej:I.Rttt+i51{$1
= jut.-(J-.T1-;=ftYT)))HL.I i.7-I:.Lil !t)(:, !Li!F.I.J5i.1S jgJ)
B*BBi8=b,V'T, #L= CDllc BBJr&#PB5JirCIDObS&kfR L,TUlf=o
@ wT 3b-iUuDO-KO 8= LP-BM5 dS%i&, B*BB&*W$lJJr&9--1 i,*Jl yjs'ctUt> type I -1'y9-7 I tj y
-1l-(type I IFNs) 0) mRN^ HiiiktEg{BeL,f=.mpSu.r&iJ--ITt*-/ y8=#%ti2;k-#hbtib,-3f=bS, i
Rk1& 8 iqn IDO-KO a) type I IFN s mRN^ A-Ej:5T1%8=teuDL,TV,f=. 5 68=, CDllc BBJrB#M5}iO)f%
i(i_i.ii!J:-[Po)type I IFNs ;D1/J=,iiiEj:WT C=tEQ& LT IDO-KO j3'ctU;1-MT 8=i3U,T#%8=tmD LTV,
@ Type I IrTNs 0);Dj2/Jig:[17JJ'da)i.a.Li:-{lT.[j:,)T.ZfL--'f3:Iu]J5TiE1-,3;#J4*/SmD&75SwT i tEFEkLT IDO-KO T^E%8=fuD
L/CU'f=. 3:.[g,S,IL)0-KO 0)lJ(.4..J1:[I)]rBl1.llhtif)hiEi,ConA *u.i7%f-etWT
ct9 #%8=tBhD LTU,flo
@ I.P-BM5 91)i,A-iii-tj:, I.itBn1&8 iuT. IDO-KO iblctU( l-MT B*BiHgRq]n9-I}t,x%Ej: WT
ct9 #%8=
1BtfL,TV'f=. a 6C=, IL)0-KO jt;cEUi'I-MT L=33'U,-CtghDLf= type I IFNs 0)btt>/}t,RlfRk
8RjaBla f=bL=, WT 33i:U;1I)0-KO 7ul6 0))]'.1'-,1:LI7]1Lai type I IFNs 0)**RKI4=-eBaS Lf= i I a,
[TrfI]l.)'t(t=it..f:))[Tir1'.::I_i31
tT , '(1-.TIT:l= (7 / )L 7, ])T()'Jt;1..l')))HL,7=3
6) LP-BM5 *4AB%b 8 U'Ej: LP-BM5 i 7: gond1'1' 0)=iEFBqn-ejlt'/i,i:1fjE L,TfErf*0)tE#T9eklil
floLP-BM5 *4&B%fj=1/i,8=ib'U 'T IDO-KO Ej:WT i tEg.7t}L,T4=GTj1-*bSiuPIEgr6]8=b-3 flo 3: f=,
=fEdS%ff>)i,8=h'VIT, IDO-KO 3b'iU:1-MT Gj:WT
ct9 #%8=fE#*e)ighpk,i5 L,flo
[%*]
*W5*n8=33V'T, 7 9R i/ T,t= 9-1'/I,REgB%8=blLla IDO 0)9(&jbliU(PR%Gj:, B*BE5*-c>n#3#
#n])JBf.7;1L{l:rJt;I:[IIJ)BltlJ))IH=
,i73 t)rr)i, 1 1[TNs a)J1.''t])n;Ii:1 I , (}J1' )LA
_'r)i_:,liJJ)-T).liuL
-i,i J3 I
LJ-)'Jt;[1-I(I,,.iL9.cTt i L7=. c)?-I;:,.I;,II)0 L7)ll.Y1))FIE+i).-'lf3TrL T)-/ f,7 -I. >,U)fl_tf;IJ:i.)TGJI
a);;I:[unhZ=J3t:+,TJJ1:LIJ)JhJL'i]l,g],+I,A5(i:
t-Q-#tLI1)Jh-,/JEt'=.:.3q'.< I1;FN)))1;L{,),=i)I i ,
c:.r3 :I, 7, U 7' 7,7 T > [Li.:Lqfi!-F-_4b(=Jl31!+,3r['f-.1&-bWLli'tJn)Jh-:,i)--.:.rt:I
tt 9 #PB&5EkST%&=+I tbSh]6nTUl8o HIV klj:t=b, i, Ttt= 9/}L,RLgBgk2fo)9a#Su4#ii&1#
tj:#7:t>PB6b,relj:t3:< , *WgE8=jb'U'T, I/ f.t= 9//VRZiB%8=h'Lla f, U 7o Tt77 yfe=g4JtU, 5
lj'TrL i lft3if-''f;-)JllrTf^MltliJ)--?
,lr)I,'J:1I-F1)]L 7=I i fj:, ir-rrL iltif7J/.i,li+uU.I.iJ3'.iU'1ju3ARJ=H+M)I iE-%T-Tt,J(r)73 i =F;. k6YL,flo
[*i&]
LP-BM5 BB%?9R8=b'UIT, IDO n9(tBh'ctUt>PRStj: type I IFNs i:fuP5if, 9-Ill,R%k]q
''[J:1H-7JI.i ,Jl-fFL fL- i!,:-lll-LLJ L rL., 7, T)7 T,7 7. >(L1.i4ni7FZ'(:-'f-;7:[nTL!1,i:-Fi.-r.1)t3:[lHJBu)l'k#!t,t,),I3U,.'Tt#.[7UJbi
I)EE=riT{_7!)I[r1:='A;tL1'f-kL'.1;:rJ'ir,ili-7.'=L I i,
,T3LL.]=,-ii3i.Lf=,, .Shf.1Li,7, 7)7 f,7 7p > rt-i;it'JuL}tJl,-H)i-i:rl7)JBv):fi.u
f1-I)T,krfltia)(fp)Py]/J;
Jet-R-Lit(i-f)8.,
i&X%iO)#5EO)fB
*i#% a #^Ej:, LP-BM5dS%79R8=b'U,-C, IDO n9(&klU:7RSIj:type I IFNs i:tuD5
if, t>-J}L,R%kWSTJi-8 I i kPB 6b,8= Lf=. *W9hji=tj:,I/ I,t= 9j)I,_RB%?TK8=hlL183t2iS[J
illTf^nl1.'ia)
--Iir!.i,+i-[q71!.UIL f= 'i,v) Tt, .,'tTi-ri=1f_LIL:/Ut't:I:][r,tJ:T'gillL):i1![r]:IW-DiJ?I:a)1EDii-:I ,JjhjLL1?.)"L) T3tl:i',;--A--+,T3 Ju
a)i.iP,LIJ)73_,
[=i=_.i--I:i7i- 1ti;:;;:.i:A
Masato Hoshi, Kuniaki Saito, Akira Hara, Ayako Taguchi, Hirofumi Ohtaki, Ryo Tanaka, Hidetsugu
Fujigaki, Yosuke Osawa, Masao Takemura, Hidetoshi Matsunami, Hiroyasu Ito, Mitsuru Seishima :
The absence of indoleamine 2, 3-dioxygenase upregulates type I interferon production
resulting in suppression of viral replication in retrovirus-infected mouse
Journal of Immunology l85, 3305-3312 (2010)