ƉunɂP퐫̈ێƐ䐫TזE

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emailF<a href="mailto:mhamaguchi@ifrec.osaka-u.ac.jp">_^p</a>
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̈Zr[, <strong>2</strong>, e005 (2013)@<a href="http://dx.doi.org/10.7875/leading.author.2.e005">DOI: 10.7875/leading.author.2.e005</a>
Masahide Hamaguchi & Shimon Sakaguchi: <strong>Mechanisms of regulatory T cell mediated immune suppression.</strong>

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<h2>v </h2>
@ƉunɂP퐫̈ێɂẮCƉu}@\ɓזEnł鐧䐫TזEdvłD䐫TזEɂƉu}̒SIȋ@ƂāCC^[CL2̎Y}CCD25̔ɂC^[CL2̌͊CCTLA-4̔ɂR񎦍זE̋@\}Dɂ킦CC^[CL10̎YȂǕIȗ}@\͂炭ƍlĂDŋ߂̌C䐫TזE͎ᇖƉuڐAƉuȂǂɂ邳܂܂ȐI邢͕aIȖƉu̐C܂CƉuP퐫̈ێɕK{ł邱Ƃ炩ɂȂĂDC䐫TזEWIƂƉu̎Ö@ї\h@C܂CƉu𘴐i邢͌コ@̊JɂĐvȐiW҂D

<h2>͂߂</h2>
@ȖƉun͕aȂǂ̕âɉʓIɔr邪C̂\鐶̕qC׋ۂȂǂ̋C邢́Cɑ΂Ă͉ȂDCȂ\镪qɑ΂ƉusjꎩȖƉuNƁCȖƉu̔ǂɂD܂Câɑ΂ƉułĂCꂪߏłΑgD̏QƂȂƉuawIȎ̌ƂȂDƂ΁C׋ۂȂǂ̋HaRɑ΂ߏȖƉu͉ǐ̌̂ЂƂłD܂CԕȂǖƉuwIɖQȊɑ΂ߏȖƉu̓AM[NDł́Ĉ悤ȖƉuȊe邢͖ƉuP퐫ێ鐧@\ɂāC䐫TזE̖𒆐Sɍŋ߂̍lD

<h2>1DƉuȊeіƉuP퐫̈ێƐ䐫TזE</h2>
@ƉuńgȁhƁg񎩌ȁh̖ƉuwIȎʂ̋@\ƁCɂƂÂƉuȊe̓іƉuP퐫̈ێ̋@\DƉuȊeƂ͎ȍRɑ΂ƉusD̂悤ȖƉȗ\Iȋ@\ƂāCȔp̑̕IDBɂẮCBXg[}זEɂ񎦂鎩ȍRyv`hNHCqƂ̂̕𖢏nȎȔTזEFƁCTזE̓A|g[VXɂDȂ킿CB⍜ƂSpY튯ł͎Ȕp̑IɂrĂDȂCׂĂ̎Ȕpr킯ł͂ȂDہCȍR͂ȃAWogƂƂɖƉuΎȍR̂邢͎ȔTזEeՂɗUłDȂ킿CݓIɎȖƉuN鎩ȔṕCȌ̖̂ƉunɐIȏԂő݂D̂悤ȎȔp̊ёB}鐶IȐ@\̂ЂƂ́CTזEɂ}IȐłD
@Ɖu̗}IȐ@\ɓTזE݂邩ۂC݂ƂĂُ̈킪Ȃ炩̖Ɖǔł邩ۂɊւẮCc_<a href="#R1"><sup>1)</sup></a>D̉𒼐ړIɏؖ̂ЂƂ́CȓTזËQ邱Ƃɂ莩ȖƉuȂǂ̖ƉuUł邩CTזËQȂƂł̖Ɖu̔ǂ}ł邩C邱ƂłD̂悤Ȏ݂ƂāCȃ}EXB璲TזECD25iC^[CL2ẽj𔭌CD4zTזECTזĚ铯ñ}EXiƂ΁CVIɋBk[h}EXjɎcTזEړƁCړ2`3JŎȖƉubBCȖƉu݉CI^AaȂǂ܂܂ȎȖƉuɎRǂ邱Ƃꂽi<a href="#F1">}1a</a>jD̎ȖƉu̔ǂ́CCD25zCD4zTזE̓ړɂ芮Sɑj~ꂽD̂悤ȎȖƉu̔Ǒj~\CD25zCD4zTזÉCȌ̂ɂĖCD4zTזE̖10߂ĂC䐫TזEƖÂꂽ<a href="#R2"><sup>2)</sup></a>D܂CCD25zCD4z䐫TזE͐ȋBɂċ@\IɐnԂŎYDȂ킿CȋB́CȖƉuN鎩ȔTזÊ݂Ȃ炸C̊ёB}鐧䐫TזEYDƉuȊéCȔTזEɑ΂镉̑Iɂ킦C䐫TזEɂ\Iȗ}ɂێĂ<a href="#R3"><sup>3)</sup></a>D

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@Foxp3z䐫TזEɂƉuȊëێƂُ̈</strong>
iajȃ}EXɗR郊p琧䐫TזEiCD25zTזEĵk[h}EXɈړƁCȖƉu≊ǐȂǂ̖ƉuRǂD
ibjqgIPEXǌQł<em>FOXP3</em>`q̓ˑRψق̌ʁC@\̐䐫TזEĂĎʁCȖƉu≊ǐCAM[ǂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/05/Sakaguchi-2.e005-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2013/05/Sakaguchi-2.e005-Fig.1.png&amp;caption=fig1-caption-text]


<h2>2DCD25zCD4z䐫TזEƓ]ʈqFoxp3</h2>
@Ɖunɓ݂CD25zCD4z䐫TזȄdvȓƂāC]ʈqFoxp3ٓIɔĂCFoxp3̌邢͓ˑRψقɂ萧䐫TזE̔ѕC܂C}@\Q邱ƂD<em>Foxp3</em>`q͒v̎ȖƉuщǐRǂScurfy}EX̌`qƂă|WViN[jO@ɂXF̂ɂē肳CÂāCƂłׂ̂qgIPEXǌQ̌`qł邱Ƃꂽ̂ł<a href="#R4"><sup>4)</sup></a>D܂CTזEłFoxp3ُɔ邱ƂɂƉu}@\ƂʂC<em>Foxp3</em>`q͐䐫TזE̔ы@\ɂ}X^[`qłƍlĂ<a href="#R5"><sup>5-7)</sup></a>D
@䐫TזȆ݂͓ɂؖꂽC䐫TזEƉuȊe邢͖ƉuP퐫̈ێɕsȖ͂Ă邱Ƃ̒ړIȏ؋́CXF̔򐫂̈`łIPEXiimmune dysregulation, polyendocrinopathy, enteropathy, X-linkedCXF̘AƉuُ푽QajǌQ݂̑łD̒P̈`qψقɂḦ`ł́CI^Aa80CȖƉubB70ĈقCnnCaȂǂ܂܂ȎȖƉu3NȓɔǂDقƂǑSɂĉǐǂC܂CƉuOuEǁCAM[畆CHAM[݂DIPEXǌQ̌`q͂ɏqׂ<em>FOXP3</em>`qłD<em>FOXP3</em>`qɓˑRψقƂ̑唼ɂĐ䐫TזE̔jQČʁCȍRє񎩌ȍRɑ΂Ɖu̐䂪ُ<a href="#R8"><sup>8)</sup></a>i<a href="#F1">}1b</a>jD
@]ʈqFoxp3ɂ`q̐@\̉𖾂́CBŎY鐧䐫TזE̔ы@\̗݂̂Ȃ炸ClHIFoxp3z䐫TזE쐻邤łdvłDہC}EX̃iC[uCD4zTזETGF̑݉ɂčRɂhFoxp3𔭌C@\ѕ\^ɂēݐ̐䐫TזEɗގU䐫TזEIɍ쐻łDCݐ̐䐫TזEƗU䐫TזEƂ͋@\IɊSɂ͓ł͂ȂƂĂ<a href="#R8"><sup>8,9)</sup></a>Dݐ̐䐫TזEƗU䐫TזEƂ̍ő̍ق́CTזEê̍RِFoxp3̈萫łDȂ킿CU䐫TזE͎ȍRɑ΂ea̒ႢiC[uCD4zTזE番邽߁ĈƎȔF\ႭȂD̂Ƃ́CȖƉu̍זEÖ@ƂėU䐫TזEp邱ƂɂĂ͕sɂ͂炭CCڐAЂɑ΂ƉueڕWƂזEÖ@ł͗Lɂ͂炭ȂDCU䐫TזEɂFoxp3͕̔słĈƂՏւ̉p͂΂ł<a href="#R9"><sup>9)</sup></a>D
@ߔŇɂCU䐫TזEɂFoxp3̕s萫́C<em>Foxp3</em>`q̃GsWFleBbNȐ̈ႢɗRƗĂ<a href="#R9"><sup>9-12)</sup></a>DGsWFleBNXƂ́CDNAz̕ωƂȂ킸זÊ̂p`q邢͕\^̕ωƒ`C`q̃GsWFleBbNȐƂ́CDNA̔z͕ω邱ƂȂDNAN}`̏Cɂ`q䂳邱ƂłDߔNCזEnɓٓIȈ`q́C]ʈqɂ鐧ƃGsWFleBbNȐɈˑ邱Ƃ炩ɂȂĂĂD䐫TזEɂGsWFleBbNȐƂāCFoxp3͂߂Ƃ鐧䐫TזEɓٓIȂ܂܂ȋ@\^pNR[h`q̔̈ɂāC䐫TזEɓٓIȒE`݂̈̑邱ƂDU䐫TזEł<em>Foxp3</em>`q͂߂Ƃ鐧䐫TזEɓٓIȈ`qɂāC䐫TזEɓٓIȒE`̈悪`ꂽ܂܂łĈ߁C<em>Foxp3</em>`q܂ސ䐫TזEɓٓIȈ`q͕̔słD݂ł́C䐫TזElHIɗUɂ͒PFoxp3𔭌΂悢ƂiK͏ICFoxp3Iɔ邩ƂiKɓĂD
@܂CqgCD4zTזETזEêɋhƔrIeՂFOXP3𔭌邱ƂmĂ邪Ĉ悤FOXP3zCD4zTזE͐䐫TזEɓٓIȒE`̈悪E`Ă炸CFOXP3͕̔słCɁCƉu}@\Ȃ<a href="#R13"><sup>13)</sup></a>D䐫TזEɓٓIȃGsWFleBbNȏC𓱓邱ƂɂCFOXP3݂̔̂Ȃ炸C@\IɈȐ䐫TזE쐻@̊J]܂D

<h2>3D䐫TזEɂƉuP퐫̈ێ̕q@\Ƃُ̈</h2>
@ɏqׂ悤ɁC䐫TזECD25iC^[CL2ẽjĂ<a href="#R2"><sup>2)</sup></a>DCD25́CC^[CL2ẽłCD122уC^[CL2ẽłCD132ƂƂɁCC^[CL2ê\D䐫TזÉCBɂŶƂ炷łɍeãC^[CL2ê𔭌قTזEłDC䐫TזEł͓]ʈqFoxp3C^[CL2`q̔}ĂĎʁC䐫TזE̐̈ێɂ́Cق̍זEɂYC^[CL2słDۂɁCC^[CL2mbNAEg}EX͐䐫TזËُɂv̎ȖƉuǂ𔭏ǂ<a href="#R14"><sup>14)</sup></a>D܂CȌ̂ɃC^[CL2̒aR̂𓊗^ƁC䐫TזEȖƉuRǂ<a href="#R15"><sup>15)</sup></a>DāCCD25͐䐫TזÊ悢}[J[łƓɁC䐫TזE̋@\ɕK{̃^pNłDɁCقTזEɂC^[CL2ʂɎYƁC䐫TזEBƉu}i邱ƂɂCȂƉu}DȂ킿CC^[CL2͕̃tB[hobNɂƉu}Ăi<a href="#F2">}2</a>jD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@Foxp3z䐫TזEɂƉu}̕q@</strong>
]ʈqFoxp3́CRunx1NFATȂǂق̓]ʈqC^pNC}^pNƂƂɓ]ʈq̂`C܂܂Ȉ`q̊𐧌䂵ĂDȂłC<em>Ctla4</em>`q̊C^[CL2`q̗}dvłD䐫TזE̔CTLA-4́CR񎦍זEɂCD80/CD86̔Ⴍ}邱ƂɂCقTזE̊ɕKvȕh񋟂łȂ悤ɂĂD܂C䐫TזE͍eãC^[CL2êC͂C^[CL2󂯎邱ƂɂCقTזEC^[CL2D̊܂D䐫TזE͕̖Ɖu}@\CƂdvȋ@͍R񎦍זECƂɎזEɂTזE̗}łD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2013/05/Sakaguchi-2.e005-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2013/05/Sakaguchi-2.e005-Fig.2.png&amp;caption=fig2-caption-text]

@䐫TזE͕̋@ɂƉu}\𔭊邪C䐫TזE̖Ɖu}@\͍̍R񎦍זEɂTזE̗}łDiC[uTזE͍R񎦍זECƂɎזE̒񎦂RɂTזEêւ̎hiVOi1jƁCR񎦍זEɔCD80/CD86ɂCD28ւ̕hiVOi2jɂ芈CC^[CL2YBD䐫TזȄdvȓƂāCCD28̕qzOłCTLA-4˂ɍĂ邱Ƃ<a href="#R16"><sup>16)</sup></a>DCTLA-4CD28ƓCD80/CD86ƌD̐eaCTLA-4̂قCD2820{D䐫TזEɔCTLA-4͍R񎦍זEɂCD80/CD86̔}ĎʁCR񎦍זE͍R񎦂Ăh񋟂łȂ߁CقTזEłȂ<a href="#R17"><sup>17)</sup></a>i<a href="#F2">}2</a>jDɁCɏqׂ悤ɁC䐫TזE͍eãC^[CL2êC͂C^[CL2󂯎邱ƂɂقTזE̊ёBɕKvȃC^[CL2DCRTזEɃA|g[VXUDɁC䐫TזȄ͓iƂ΁CǔSjɂĖƉu}̃TCgJCłC^[CL10YDC^[CL10͂ɍR񎦍זE̐n}邱ƂɂƉu}Ɋ֗^<a href="#R18"><sup>18)</sup></a>D܂C䐫TזE͉ǂ̃^CvɉĖƉu𐧌䂷邱ƂłDƂ΁C{Iȗ}ێCTh1^̉ǁiƂ΁CC^[tF̎Yjɉē̃PJCéiƂ΁CCXCR3j𔭌CTh1̏ɓĂŖƉu}\𔭊D

<h2>4D܂܂ȐIѕaIȏԂƐ䐫TזE</h2>
@䐫TזE͖ƉuȊëێɕKvTזEƂĔꂽD̂̌ɂC䐫TזE܂܂ȐI邢͕aIȖƉu̐C܂CƉuP퐫̈ێɂĕK{ł邱Ƃ炩ɂȂĂ<a href="#R4"><sup>4,19)</sup></a>DƂ΁CᇖƉuɂĎᇍזEɓٓIȃp̔FᇍȒ͐ȎȍRłDāC䐫TזE͖ƉuȊeێƓɁCᇂɑ΂ƉuĎ@\゠邢͑jQD܂CᇑgDł͐䐫TזECƂɎᇂɐZTזȆ啔䐫TזEł߂邱ƂDۂɁCIɐ䐫TזE邢͌邱Ƃɂᇂɑ΂Ɖu𘴐i邱ƂłD݁C䐫TזEWIƂ邪ƉuÖ@JDŁCڐA̗źCڐAɑ΂Ȃ̑ɑ΂̂ƓȖƉueU邱ƂłDۂɁCIɐ䐫TזEڐAARɓٓIɑB邱ƂɂڐAƉueUłDɁCECXC׋ہC񐶒Ȃǂɂ邳܂܂ȊǂɂāC䐫TזE邢͌邱ƂɂƉuIɘi邱Ƃ\łD܂CIPEXǌQɂ݂悤ɁC䐫TזE̋@\ُɂ蒰ݍ׋ۂɑ΂ߏȖƉuN邱ƂCݔƂ̐IȋɂĂ䐫TזE͕K{̂͂炫Ă̂ƍlDCDP̂ǂ̂悤ɂđَeɑ΂ƉueێĂ̗̂͂܂ɖƉuw̏dvȉۑł邪CDPł͑ٔՂɑ̐䐫TזȄWς݂D܂CDP琧䐫TזEƂƂɗYNDāCَƕقɂƉueɂĐ䐫TזEdvȖ͂Ă̂ƍl<a href="#R20"><sup>20)</sup></a>D

<h2></h2>
@ł́C䐫TזE̗̔jIȈӋ`͂߁C䐫TזEÂ]ʈqFoxp3ƃGsWFleBbNȐCȂтɁCƉu}̕q@\ɂāCvȍڂɂڂD̂悤ȒmƂɁCC䐫TזEWIƂƉu̎Ö@\h@C܂CƉu𘴐i邢͌シ@̊JɂĐvȐiW҂D

<h2> </h2>
<ol>
<li id="R1"><span class='au'>Sakaguchi, S.</span>: <span class="ti">Regulatory T cells: key controllers of immunologic self-tolerance.</span> <span class='so'>Cell, 101, 455-458 (2000)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/10850488" target="_blank">PubMed</a>]</span></li>
<li id="R2"><span class='au'>Sakaguchi, S., Sakaguchi, N., Asano, M. et al.</span>: <span class="ti">Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor -chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.</span> <span class='so'>J. Immunol., 155, 1151-1164 (1995)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/7636184" target="_blank">PubMed</a>]</span></li>
<li id="R3"><span class='au'>Itoh., M., Takahashi, T., Sakaguchi, N. et al.</span>: <span class="ti">Thymus and autoimmunity: production of CD25<sup>+</sup>CD4<sup>+</sup> naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance.</span> <span class='so'>J. Immunol., 162, 5317-5326 (1999)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/10228007" target="_blank">PubMed</a>]</span></li>
<li id="R4"><span class='au'>Bennett, C. L., Christie, J., Ramsdell, F. et al.</span>: <span class="ti">The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3.</span> <span class='so'>Nat. Genet., 27, 20-21 (2001)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/11137993" target="_blank">PubMed</a>]</span></li>
<li id="R5"><span class='au'>Hori, S., Nomura, T. & Sakaguchi, S.</span>: <span class="ti">Control of regulatory T cell development by the transcription factor Foxp3.</span> <span class='so'>Science, 299, 1057-1061 (2003)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/12522256" target="_blank">PubMed</a>]</span></li>
<li id="R6"><span class='au'>Fontenot, J. D., Gavin, M. A. & Rudensky, A. Y.</span>: <span class="ti">Foxp3 programs the development and function of CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells.</span> <span class='so'>Nat. Immunol., 4, 330-336 (2003)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/12612578" target="_blank">PubMed</a>]</span></li>
<li id="R7"><span class='au'>Khattri, R., Cox, T., Yasayko, S. A. et al.</span>: <span class="ti">An essential role for Scurfin in CD4<sup>+</sup>CD25<sup>+</sup> T regulatory cells.</span> <span class='so'>Nat. Immunol., 4, 337-342 (2003)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/12612581" target="_blank">PubMed</a>]</span></li>
<li id="R8"><span class='au'>Sakaguchi, S., Yamaguchi, T., Nomura, T. et al.</span>: <span class="ti">Regulatory T cells and immune tolerance.</span> <span class='so'>Cell, 133, 775-787 (2008)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/18510923" target="_blank">PubMed</a>]</span></li>
<li id="R9"><span class='au'>Floess, S., Freyer, J., Siewert, C. et al.</span>: <span class="ti">Epigenetic control of the <em>foxp3</em> locus in regulatory T cells.</span> <span class='so'>PLoS Biol., 5, e38 (2007)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/17298177" target="_blank">PubMed</a>]</span></li>
<li id="R10"><span class='au'>Polansky, J. K., Kretschmer, K., Freyer, J. et al.</span>: <span class="ti">DNA methylation controls Foxp3 gene expression.</span> <span class='so'>Eur. J. Immunol., 38, 1654-1663 (2008)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/18493985" target="_blank">PubMed</a>]</span></li>
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</ol>
<div class="au-profile">
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<span class="author">_ ^piMasahide Hamaguchij</span>
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<strong> uiShimon Sakaguchij</strong>
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