TזE̘VƖƉuV

<strong>Mmq<sup>1</sup>E <sup>2</sup></strong>
i<sup>1</sup>swiPSזE ȊwJ񕔖C<sup>2</sup>sww@w fBJCmx[VZ^[j
emailF<a href="mailto:yoko.hamazaki@cira.kyoto-u.ac.jp">Mmq</a>
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̈Zr[, <strong>7</strong>, e005 (2018)@<a href="http://dx.doi.org/10.7875/leading.author.7.e005">DOI: 10.7875/leading.author.7.e005</a>
Yoko Hamazaki & Nagahiro Minato: <strong>T cell aging and immunosenescence.</strong>

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<h2>v </h2>
@ߔNC܂܂ȉ֘A̔ǂaԂ̌`ɖƉuVdvȖ͂Ƃ炩ɂĂĂDƉuVƂ́CƉun̉ɂƂȂὠĕ\płCނˁClƉu\̒ቺCǐf̑CȖƉuXN̑CƂ3̒ɂÂDȂ킿Cĝh䂵r鐳ȖƉuቺCǂ⎩ȖƉuiƂCʐƂɓDɂ肠ƉuזEIы@\IɕωCTזEY鋹B̋@\͑ɒቺ邱ƂCɂωTזEƂ傫ƂD̃r[ɂẮCB̑ޏkƂɂƂȂTזE̎IяWcIȕω̎ԂƋ@ɊւmЉC̖ƉuזE̋@\ɉeTזẺɂωƉuVɂ͂Ӌ`CāCƉuV̐䂨т̍̉\ɂċc_D

<h2>͂߂</h2>
@Ɖun͎Ȃ̐Ɣ񎩌ȐƂʂC׋ۂECXȂǂ̊̔̊h䂨т̔rɕK{łD_C̉p̓ɔzuĈ̂ɂ̓[זEcƂɂƉun͐nƂDȂCɂƂȂ̋@\͏XɒቺC̈ŁCǂ⎩ȖƉui邱ƂɂCӐCCȖƉuȂǁC֘ADƉun̉ɂƂȂ@\IȕϗégƉuVhƑ̂CƂɁCRِіƉuLƂlƉun̕ωłƂ邪C̕qזEwIȊՂɂĂ͂悭킩ĂȂD̃r[ɂẮCƉuזÊȂłƂ̉eƂTזẺɂωјVɂāCM҂̍ŋ߂̌܂߉CƉuV̌юԂ̗CāC܂܂ȉ֘AƂ̊֘Aѐ̉\ɂċc_D

<h2>1DTזEY鋹B̂Ȃ肽ёޏk</h2>
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@܂ł̌CB̑ޏǩ͂TזE̎YɂvȋBXg}זEł鋹BזE̕ωɋNƍlĂCqgł1΂邱납炷łɉɂῶ܂ƂD70ΑłĂqg̋B͐VTזE̎Y\ƂGrfXC40ΑŎYVTזE͐V1/100ȉɒቺƂĂDdvȖƉuזEYgD̋@\Xɒቺ͕̂svcȌۂƂ邪CB̑̑ޏk͎ۂł邽߁C̂ɂƂȂ炩̃Ahoe[W\wEĂDBɂTזE̎ỶߒɂẮĈɏqׂ鐳̑Iѕ̑ỈߒւTזEɕ̂͂ق5xłClƉun̓[זEcƂɂ肢ǊIɔr邱ƂlƁCUɂ킽VȃiC[uTזE̎Yێ邱Ƃ̓GlM[̓_D܂ȂłȂCCقǕKvȂ̂Ȃ<a href="#R1"><sup>1,2)</sup></a>D
@CB̑ޏkɐz␫z֗^邱Ƃ͌ÂmĂ<a href="#R3"><sup>3)</sup></a>D̂Ƃ́Č琶̑ɂTזE̎Yɔ₵RXgC̂̐␫nɂƂȂʂ̐̌nɎĝł͂ȂƂ͓Iȃf̍ɂȂĂDۂɁCqg̑OBɑ΂AhQÖ@ɂ薖TזEƂ̕񍐂ȂĂ<a href="#R4"><sup>4)</sup></a>DŁCɂ萫z}EXɂ鋹B͈̔ߐł邱ƁC܂CɂƂȂzቺĂB͉̊񕜂ȂƂCzȊO̍p@݂̑CˑRƂċB̑ޏk̋@\̑Se͖炩ł͂ȂD
@B͔玿Ɛ2̗̈悩ȂC玿זE͎ȂMHCqւ̉̊lȋIjCLRɉ郌pgǍ`Cwp[TזE邢̓L[TזEւ̉^ɒSDɂẮCזEƎזEƂĎȉTזȄȋIjіƉu𕉂ɐ䂷鐧䐫TזE̎YNCȂUȂȊe̐\ɂi<a href="#F1">}1</a>jDזÉCCXȂǖ{͋Bɑ݂Ȃ܂܂ȑgDRUĂ͂ȂȂȂ̐ƂTזEɒ񎦂Ƃ߂ăj[NȐĆCqg̎ȖƉuBǌQ1^̌`qYƂē肳ꂽj^pNAIRÊ͂炫ɂ̂łČn̔j]ȖƉuЂNƂ1997Nɖ炩ɂꂽD̔ȍ~CBXg}זȄdv炽߂ĔFCBXg}זE̔ы@\̕Ɋւ錤20NŔIɐi<a href="#R5"><sup>5)</sup></a>D

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@B̍\ы@\</strong>
TOזE͋B̔玿ѐɂĂꂼꐳ̑Iѕ̑IւāCiC[uTזEƂȂ薖ւƈڍsD̂̂TזE͈قȂ鉞߁CiC[uTזE͉̐R̐x܂ŔfD̑gDɂĊNƁC̍RɓٓITזEłGtFN^[TזECсC2xڂ̊ɑΉ郁[TזEւƕD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.1.png&amp;caption=fig1-caption-text]

@M҂́C}EXɂĐזE̊זE̓ɐC̏Claudin-3Claudin-4𔭌鐑犲זẺ敪CقڐUɂ킽萑זE̎YюȊeێ邱Ƃ𖾂炩ɂĂDāC犲זE̊̒ቺB̑ޏkɐsĐシƂ\z葁ɋN邱ƁCɁCTזEYȂRag2mbNAEg}EXɂẮC犲זE̊̂ɂĂێ邱Ƃo<a href="#R5"><sup>5-8)</sup></a>i<a href="#R8"><sup>8)</sup></a>  <a href="http://first.lifesciencedb.jp/archives/9645" target="_blank">V_r[</a> łfځji<a href="#F2">}2</a>jD̎CB̑ޏk̊ՂƂȂ肤鋹B犲זE̊̒ቺCɌ̂̉ɂN̂ł͂ȂCo̒̊TזE̎YɈˑ邱ƂꂽD܂ɁCȂƂ̗ʂTזE̎YɂC犲זE̊CЂẮCB̊}@\݂̑\ꂽD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@B̐犲זEɂ銈̐</strong>
BɂĐ犲זE̊͋B̑ޏkɐsďo̒ɋ}ɒቺDCTזEYȂRag2mbNAEg}EXɂẮĈł犲זE͍̊ێĂD
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@BOזEыB犲זE̓⊈̐ƋB̑ޏkƂ̂ɊւḿCB̌`sSɂV̖ƉusSǂ̎ÂCڐÂ̂TזẺ񕜂𑣐i鋹B̋@\̕@̊JȂǂւ̉p҂Ă<a href="#R4"><sup>4)</sup></a>D

<h2>2D̂̐UɂTזETuZbg̃_Ci~YіƉuV</h2>
@B̑ޏk̋@\̂̂ɂ킦Cꂪǂ̂悤ȐIȈӋ`̂𗝉邱Ƃ͏dvłDقږɑ݂関m̍Rւ̉̕ۏ؂ƖƉuL̊mlƉun̂Ƃdvȗvfł邪C̂̐UɂĂ̌n͂܂܂ȕωƂD
@TזEɒڂƁCqg̈ꐶ̂ŏ10`20NŁĈ̈قȂRِiC[uTזEiRɂ܂IĂȂTזEʂɂԁj̗ʂYClȍRɉłTזẼpgÃZbg𖖏̃pgDɔzuDɁĈтɎłGtFN^[TזEYƂƂɁC[TזEcƂɂ2xڂ̊ɐvN邽߂̌n\zi<a href="#F1">}1</a>jDĐnlƉunǂł̂́CB̑ޏkɂiC[uTזE̎YቺȂC⊮邩őBP퐫Bɂ肠x̐ΐێD܂C}łȂCEBECXTCgKECXȂǂ̐䂷D̂悤ɁCTזE͓O̎hɉێƂIȕtۂĂ邪C4`50΂肩疝ǂ⎩ȉ̑储ы@\̌オXɌ݉C75΂ƈՊ悷ȂǎۂɗՏIȈӋ`ɂȂDƉun̉ɂωN܂܂ȖƉuwIȓ𑍏̂āgƉuVhiimmunosenescencejƂсC傫3̒ClƉu\̒ቺCǐf̑CȖƉuXN̑CɂÂ<a href="#R9"><sup>9)</sup></a>DȂ킿CƉuVƂ͖Ɖu@\܂˂ʂɒቺƂƂł͂ȂCD܂ቺōD܂ȂiƂC񑊔ʐƂɓDȉC3̓ɂďqׂD
@lƉu\̒ቺƂ[IɎ̂́CɂƂȂՊъǂ̏dĉł낤DƂ΁C҂ł͔xۂCtGUECXǂւ̜늳㏸邾łȂdǉ₷߁CƂɒvIƂȂDŁCN`̌̒ቺƉuVɂlƉu\̒ቺÂ錻ۂ̂ЂƂłDN`ɂ荂҂̖Ɖu\P悤Ƃ݂͂ȂĂ邪ClƉu\𗘗pĐlדIɖƉuL`ƂN`̐ClƉu\Ⴂ҂ɑ΂ʂ͕KȂƂ̎wE<a href="#R10"><sup>10,11)</sup></a>DNȍ~C`qψق̒~ςȂǑ̍זEɂĂ͂זE₷vCƕsāC{͕ψقȍזE񎩌ȂƎʂĔrƉunXɋ@\ቺ邱ƂC҂ɂ邪̔Ǘ̏㏸Ɋ֌W邱ƂwEĂD
@ǂƂ́C̏ɂǏł̊̔rъlƉůJnɏdvȖ͂̉ƒ`DŁCIȈqɂ񊴐ɎNCɃ}Nt@[W⃊p̐ZёgD̃fOƂx̉ǁCȂ킿Cǂ̃XN㏸邱Ƃǐf̑Ƃ<a href="#R12"><sup>12)</sup></a>DdvȂƂɁC̖ǉ͂ƂɒNȍ~ɏXɑ債CAaɂCXϐCdȂǂ̐KaCӐC_oϐCtCijCȂǁC܂܂ȉ֘AɊ֗^邱Ƃ炩ɂĂ<a href="#R12"><sup>12)</sup></a>DȂCɂƂȂǐf傷@͕K悭Ă͂炸C̑傫ȌۑłD
@ȖƉuɂ͒P`qُ̈ɂcɔǂH݂邪C̏ꍇ͕̈`qъv֗^鑽qłC̃XNq̂ЂƂƂĂƂĉĂ<a href="#R13"><sup>13)</sup></a>DȖƉȕ͂΂ΌlɂF߂CƂɍ҂ɂČłDƂ΁C҂͑ނ̎ȍR̂ƁC܂C܂܂ȑւ̃p̐ZN邱ƂmĂDۂ͖̂̂炩ȎƂ͂ȂĈ̂̑ራxɏQ@\̒ቺNƂȂ\͏\ɂDȖƉuĈ悤ɖ炩ȎNƂ̂Ȃȉ̒xɑ債ʂƒPɂƂ炦ׂł͂ȂCȂƂCȉ̑f͉ɉďXɑDCNɔǂP̈`qُ̈ɂꕔ̎Cq̑̎ȖƉu̔ǎ̕ς30`40ȍ~C邢́C50`60΂ł<a href="#R13"><sup>13)</sup></a>DȖƉü`IȃXNɂƂȂ݉闝R͂܂słD
@ȏ̓_CƉuV̑S̑𕪎qx邢͍זExŗ邱Ƃ́C҂̈Պւ̑΍ʓIȃN`̊JCNȍ~̂̔ǂ̗}݂̂Ȃ炸C܂܂ȉ֘A̔ǂ̋@ѕaԂ𗝉邤ł߂ďdvłD

<h2>3DB̑ޏkɂƂȂTזE̍P퐫B</h2>
@TזẺɂω̃_Ci~YіƉuV̕qזEwIȎ̂𗝉邽߂ɂ́CXTזE̕ωCсCTזETuZbg̑g̕ωlKvDXTזE̕ωƂāCɂƂȂTזEễVOi臒lȂTזEɂȂ邱Ƃ͈ȑOmĂĎۂ́CTזEễVOỉERKE_yf̔}}CNRNA̔CɂƂȂቺ邱ƂɂƂ̕񍐂Ȃꂽ<a href="#R14"><sup>14)</sup></a>D̂ƂCXTזE̎IȕωɂƂȂlƉu\̒ቺ̈[S\ꂽ<a href="#R11"><sup>11,14)</sup></a>D
@B̑ޏkɂɂTזE̎Y͌ɒቺɂ炸CӊOȂƂɁCɂTזE̐iȂƂCTזE̐j͉ɂ肳قǌȂDƂɃqgɂẮCf͂ɂCB̑ޏk̂̂̃iC[uTזẺ敪P퐫Bɂ肨ɈێƎwEĂ<a href="#R15"><sup>15)</sup></a>C̉͗cɋB̓Eo҂KȖƉusSɂ邱Ƃ͂ȂƂƈvDȂCBEo҂͂̃N`̌ʂႭC܂CTזE͍҂ƎƂ<a href="#R16"><sup>16,17)</sup></a>D킦āCVɋBEõP[XɂāCcfЂ狹BgD炩ɍĐĂƂ̕񍐂<a href="#R18"><sup>18)</sup></a>Dȏ̓_CɂTזËێɋBǂ̂悤Ɋ^̂ɂẮCɐTdȉ͂KvłDɂC̃iC[uTזȆɎYꂽTזȆBɂ肨ɈێƂ΁CrI̗ʂ̎YÂBזECXւDȂǂ̂ق̖ƉuזEƂ͈قȂCTזEɓƎ̑傫ȓłƂD
@ʏCTזE͖ɂāC2pgD̃Xg}זEȂǂ鎩MHCqƎȃyv`hƂ̂̎̕アTזEẽVOiƁCC^[CL7C^[CL15Ȃǂ̃p̈ێɏdvȃTCgJC̃VOiɂێDCP퐫B́Cp̌ɂXTזEC^[CL7C^[CL15ɉߏɔI邱Ƃɂ쓮錻ۂłi<a href="#F3">}3</a>jDȂɋeaTזEê𔭌TזEN[͕̑Iɂ苹Bɂď̂́C̓ɂ͎ȉ̔rÎア̂܂ŁCx̃XyNgTזEN[݂D̂߁CP퐫B̉ߒɂẮC苭TזEẽVOiTזEN[iȂւ̐eaTזEN[jDIɑBƑz肳<a href="#R19"><sup>19,20)</sup></a>i<a href="#F4">}4</a>jDȏ̂ƂCP퐫B̓pgA̕ΌыƎȉN[̌Iȑ炵CꂪClƉu\̒ቺ⎩ȉ̑f̑Ɋ^\wEĂDC̎ȖƉũ}EXfɂčP퐫B̔ǂɕK{łƂ񍐂<a href="#R21"><sup>21)</sup></a>CGrfX͎ȖƉü`IȑfԂւߒɂāC邢́CmŔƂCqgɂ鑽̎ȖƉu̔ǂ̎ԂƖȂD

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@P퐫BɂTזETuZbg̕ω</strong>
ɂāCTזE͎MHCqƎȃyv`hƂ̂̎̕アTזEẽVOiуTCgJC̃VOiɂێDB̐VTזE̎YƁCTזẼTCgJC̗ʂVOi葽邱ƂɂȂP퐫BЂNDP퐫Bɂ肳܂܂ȋ@\IȓTזETuZbgDiC[uTזẺ敪ɂP퐫Bɂ蕪TזETuZbg݂D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.3.png&amp;caption=fig3-caption-text]

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@P퐫Bɂ鎩ȉTזȆ</strong>
P퐫B́CMHCqƎȃyv`hƂ̂̕TזEẽVOiуTCgJC̃VOiɈˑ邽߁C莩Ȃւ̐ea̍iȉ́jN[̑ɂȂD܂CpIȑB͍זEVȂǌX̍זẼxł̕ωND
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.4.png&amp;caption=fig4-caption-text]

@CqgɂĂTזE̐ƂƕKv\ɂ邽߁CP퐫BɂTזẼpgA̕Ό͂x͐̂́CiC[uTזẼpgȂlim̕âɉ\́j͉Ă\ɈێCpgAsƂ}EXƂ͈قȂƂwE<a href="#R15"><sup>15)</sup></a>DČ̂قƂǂ͌ȍ҂̖̌̂p̂łCpgAɉߓxɕΌ炷P퐫BNCXgXȂǂɂߓxɃp󋵂Â肷邱ƂɂC̃zIX^VXj]Ă鎖Ԃz肳DtCɂ鍂҂CLTזẼpgAɂƉuĎdvȖ͂ƍl邪̊҂ȂǂɂāC늳܂ɃiC[uTזẼpgȂl\ɕۂĂ͍̂̌ۑłD

<h2>4DɂƂȂTזETuZbg</h2>
@TזETuZbg͉ƂƂɂ̍\ωDB̑ޏkɂiC[uTזECɂ2xڈȍ~̊ɑ΂\ɂ郁[TזẾCƂ傫ȍ\̕ω̗łD܂CP퐫B̌ʁC[^̍זE\ʃ}[J[𔭌<a href="#R22"><sup>22)</sup></a>CGtFN^[@\̘iTזE邱ƂCOR̎hĂȂo[`[TזEƖÂꂽTזE[^TזÊȂɊ܂܂邱Ƃ킩Ă<a href="#R23"><sup>23,24)</sup></a>D܂CɂƂȂ䐫TזEƂ̕񍐂<a href="#R25"><sup>25)</sup></a>D͂炭CgD̎ȉǂɉ}ƂƂɁCȊlƉu\̌ɂ^̂ƍlD
@M҂́CɂƂȂTזETuZbg̍\̕ωɂă}EXfpĉ͂CɉďoITזETuZbg𓯒肵ĂDV֘ATזEisenescence-associate T cellFSA-T celljƖÂꂽ[^̃wp[TזÉC}ePD-1TNFX[p[t@~[ɑCD30LiCD153j̔ɂÂDV֘ATזETזEêւ̎hɑ΂Bwp[TזEɂēT^IȃTCgJC̎YقƂǎȂɂ炸CIXeI|`Ȃǂ̉ǐ^pNCCCL1Mip-1/Ȃǂ̉ǐPJCʂɕ傷Ƃj[NȐ<a href="#R26"><sup>26-28)</sup></a>DV֘ATזE͑B̒~ɂ킦čזEV̓ƂC̓IȌ`̓wp[TזEɂזEV֘A`isenescence-associated secretory phenotypeFSASPjłƍlDᇗ}^pNMenin}EXTזE͍זEVɋNƂ񍐂ȂĂ邪<a href="#R29"><sup>29)</sup></a>CɂƂȂV֘ATזȆMenin̔̑ɂ̂ɂĂ݂͌̂Ƃ떾炩ł͂ȂD
@V֘ATזẼ͎}EXɂĂB̓Eoː̏Ǝ˂̂̂TזEړ邱Ƃɂ}ɑ<a href="#R30"><sup>30)</sup></a>DāCP퐫BߓxɋNʂƂėUꂽ\D܂Cp̌ff̂ЂƂƂ鎩ȖƉułSgGe}g[fX̃f}EXɂẮCV֘ATזEƓl̓TזEǂɐsĎŋ}ɑ<a href="#R27"><sup>27)</sup></a>D̑SgGe}g[fX̃f}EXɂĂ͎ȍR̂̒ɂ菝QNtɂV֘ATזEɎזEF߂ȂǁCp킾łȂ̂܂܂ȑgDɘV֘ATזE݂<a href="#R27"><sup>27)</sup></a>Dɍŋ߁CV֘ATזE͍bH𕉉ׂꂽbgDɂĂɑCǂNƂɂCXϐȂ2^Aa̕aԂ̌`ɂ^邱Ƃ炩ɂꂽ<a href="#R31"><sup>31)</sup></a>DזEV͉ߓxȑBɂeA̒ZkłȂCDNAN܂܂ȃXgXɂЂNꂤ邪C⋹B̓EoɂP퐫BƂȂȂ󋵂ɂĘV֘ATזEl̍זE@\́Ĉ݂Ƃ떾炩ł͂ȂDɂCȏ̌ʂCNȎ̃}EXɂ͂قƂǑ݂ȂV֘ATזȆΓIȑƉuV̈ƂȂC֘A̔ǂѕaԂ̐Ɋ^\ꂽD
@܂CM҂́CBEo邱ƂɂP퐫B郂fpāCCXCL9CCXCL10CCXCL11ȂǉǑɂčPJC̎êłCXCR3𔭌CTזEêĥZԂŃC^[tFTNFȂǂ̉ǐTCgJC𔭌CVȃiC[uCD8zTזE𓯒肵<a href="#R32"><sup>32)</sup></a>DCXCR3z̃iC[uCD8zTזE͍P퐫Bɂ蕪Û́CזEV͎̓iC[uTזE̓ł鍂B\ێĂCTזE畆fɈړƉǉɑ<a href="#R32"><sup>32)</sup></a>Dqgɂl̋@\IȓTזẺ敪݂C̊͌20`30ἉrIႢlłĂ̊Ԃł߂ĈقȂĂ<a href="#R32"><sup>32)</sup></a>D̃ocLǂ̂悤ȗRɂ̂C܂CX̖ƉȕԂ⏫Iɉ֘A̔ǗƂǂ֘Â͍̋[ۑ̂ЂƂłD
@܂ŏqׂ悤ɁCɂƂȂiC[uTזẺ敪у[TזẺ敪ɂ͂܂܂ȓTזETuZbg邱ƁC̑ΓIȑɂƂȂTזẺ̕ϗeɊ^\̂邱Ƃꂽi<a href="#F3">}3</a>jD

<h2>5DqgɂTזE̘Vт̐</h2>
@qgɂẮCCD27CD28Ȃǂ̕⏕hê̌CсCi`L[זEȂǎRƉun̍זẼ}[J[^pN̔ƂTזẺ敪ɂƂȂΓIɑ邱ƂmĂDTזETuZbǵCɍxɕTזẺ敪Ɋ܂܂CRĥ̂̑B\ႭeAZŁCTCgJC̎YזEE\͂ނ덂ƂCVisenescentjTזEƂĒ`Ă<a href="#R33"><sup>33,34)</sup></a>D̉敪̃pgA͍xɕΌĂCTCgKECXȂǂ̐ECXɓٓIȃN[𑽂܂ށD̂߁CƂނeʂ̃ECXRɎIɒI邱Ƃɂ蕪敪ƍlĂCۂɁCwɂĂTCgKECX̔񊴐҂ł͂̉敪TזE͏ȂX<a href="#R33"><sup>33)</sup></a>Dȍ҂ɂăTCgKECXEBECX̐͗ՏɂĖ̂ȂƂlƁCECX̍Ċ}邽߂ɋ@\͎cCٓIȃN[̉ߓxȑB}邱ƂŃpgȂlۂ߂݂̂ƍlC̎TזE̘V̕\^͗ǍDȓKԁC邢́CECX̍Ċ𐧌䂷邽߂ɖƉun͂炤s̑ΉƂׂ̂ł낤<a href="#R35"><sup>35,36)</sup></a>D
@ŋ߁CqgTזE̘Vp38̊ɂϋɓIɈێ邱Ƃ炩ɂꂽDTזE̘V̉ߒɂāCזEɂOR[XZxDNȂTAB1-AMPK̂mCp38IɊƂ񍐂Ȃꂽ<a href="#R37"><sup>37)</sup></a>DdvȂƂɁC̋@\ɂ鑝B\e[[̊̒ቺ́Cp38̊oHᕪq<a href="#R38"><sup>38,39)</sup></a> shRNA <a href="#R37"><sup>37)</sup></a> ɂՒf邱Ƃɂ񕜂Dȏ̌ʂ́Cqg̘VTזÉCۉזE̍זEVicellular senescencej̉ߒɂF߂stIȑB̒~̑OiKł\C܂C̗]n̂邱ƂӖDɍŋ߁Cp38ƕ̂`ZXg̋@\jQ邱ƂɂCRٓIȉуN`ɑ΂鉞񕜂邱Ƃꂽ<a href="#R40"><sup>40)</sup></a>DCTזE̘V̑lȕq@\ɏڍׂɖ炩ɂCʓIȃN`̊JȂǁCƉuV̕\^𐧌䂷@_̊m҂D
@VTזEƓlɁCB\̌サTזETuZbgƂĂ悭m敾iexhaustedjTזE̓TCgJC̎Y\サĂCPD-1Ȃǂ̗}ê̔ƂDqgƉusSECXiHIVjCC^̉ECXCB^̉ECXȂǁCrIeʂ̍RhÂɂUƂC炭̔e̍RɓD敾TזEɂ鑝B\ы@\̒ቺ́CPD-1Ȃǂ̗}êƃKhƂ̑ݍpjQCȒ݂Ȃʂ̌̂Ɉړ肷邱Ƃɂꕔ񕜂Ĉ݂Ɖu𑝋`FbN|CgÖ@ƂĉpĂDƉu͏ňłCߓx̖Ɖȗ͎gDQ邽߁CƉu̓x𐧌䂷nƂTזE̔敾̋@\݂ƍlĂCRȂȂTזEƂ̋@\IȏԂɂǂ̂ÓłD̂悤ɁCVTזEє敾TזÉCB\Ƃ_ł͋ʂĂ邪C̋̕@\זȄԂё݈Ӌ`قȂĈ̂ƗĉɂƂȂƉu̕ϗeɊ^̂ƍl<a href="#R33"><sup>33,35)</sup></a>i<a href="#F5">}5</a>jD

<a name="F5"></a><div id="fig5-caption-text" style="display: none;"><strong>}5@qgɂVCD8zTזEє敾CD8zTזE̓</strong>
iajVTזED
ibj敾TזED
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.5.jpg" target="_blank">[Download]</a></div>[hs_figure id=5&amp;image=/wordpress/wp-content/uploads/2018/06/Hamazaki-7.e005-Fig.5.png&amp;caption=fig5-caption-text]


<h2>6Dqg̖ƉuV̐ɂނ</h2>
@܂ŏqׂƉuVɊւeɊ֘AāC݁Cc_Ă_ƉuV鎎݂ɂďqׂD
@<strong>TCgKECXVTזE͔rׂH</strong>FECXɂƂȂƉu\̕ϗeɉê͂܂Ȃł낤DCTCgKECX̊₻̌ʂƂĕVTזEƉuV𑣐iƂ񍐂Cŋ߂̌ɂĂ͔ےIȕ񍐂łDȂłClɂĂ͂ނTCgKECX̊҂̂قCtGUN`̌ʂƂ񍐂͑傫ȃCpNg炵<a href="#R41"><sup>41)</sup></a>Ďʂ́C̂Nł邩TCgKECX̊̓bgƂȂ肤邱ƂĂCނC׋ۂ̂悤ɐỉߒŊlCƉu𕊊ghƂƂ炦ׂł͂ȂƂ߂ȂĂD
@<strong>p38jQ</strong>Fp38VOi̓TCgJC̎Yɂďdvł邽߁C܂܂ȉǐɑ΂p38jQ܂̎{ꂽD̓^͊̓Ő̂ߕs\łCזEVjQ邱Ƃɂ茜Oꂽ̔Ǘ̏㏸͔F߂ĂȂDp38̑jQPD-1̑jQƂ̑IȌʂ񍐂Ă邱Ƃ<a href="#R39"><sup>39)</sup></a>CƂɃN`₪̎Âɂߐ̖Ɖu̕ړIƂāCC\<a href="#R34"><sup>34)</sup></a>D
@<strong>p}CV</strong>F̉ɌʂƂmTORjQ܂ł郉p}CV65Έȏ̍҂ɓ^邱ƂɂC̃wp[TזEуL[TזEɂPD-1̗zቺƂƂɁCCtGUECXɑ΂郏N`̌ʂ㏸Ƃ̕񍐂ȂĂ<a href="#R42"><sup>42)</sup></a>DCp}CV͑ڐA̍ۂɖƉu}܂ƂĎgpĂ邱ƁC̍זEɑ΂lȍp̂邱ƁC܂Cqg̖ɂPD-1z̉敪hETזE܂ނƂȂǂCp}CV̕WIƂȂזECgpCp@ɂāCȂڍׂȉ͂҂D

<h2></h2>
@TזE̘V́CB̑ޏkɂƂȂTזE̎Y̒ቺCсC}CCɉߒɂāĈ̑ŜɂzIX^VX𐶊Uɂ킽ێ邽߂ɋN邠̓KłƂCKsƂiKȂȂƂjɖƉunɕssNCƂɕaԂƂČƂƂ炦DɂCƂqg肵₷ޗ̂ŁCTזE̘V̓}EXɂ킦qgɂĂqxł͓̐IȌi߂ĂDȂC܂ł̒m͂قƂǌl̖pēꂽ̂łCƂ΁CtC̏ԂɂqgŃpgA̋Ȃǂ݂͂Ȃ̂C܂CRz[gȂǂpāC₳܂܂ȉ֘A̔ǂ܂TזE̘V̏Ԃ͂ǂȂĂ̂CƂ_𖾂炩ɂ邱ƂKvł낤DɂCЂƂЂƂ̖ƉuV̏Ԃ\oCI}[J[̓\ɂȂƎvD̈ŁCTזE͑SgTזÊꕔłCTזE݂钰ǂCߔNCił̍őOŐ키gD풓^[TזẺɂωC܂CVTזE̓Iɂǂ̂悤ɉ֘AƂ̂ɊւẮC݁CقƂǖ炩ɂĂȂDgDxь̃xɂ͂TזE̘V̕q@\̉͂ɂẮC}EXf傫vł낤DēꂽḿCƉuVƉ֘A̗\hюÁCɂ́C҂̖ƉuԂ̓ɂN`헪̊JȂǂɑ傫v̂Ɗ҂D

<h2> </h2>
<ol>
<li id="R1"><span class='au'>Shanley, D. P., Aw, D., Manley, N. R. et al.</span>: <span class="ti">An evolutionary perspective on the mechanisms of immunosenescence.</span> <span class='so'>Trends Immunol., 30, 374-381 (2009)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/19541538" target="_blank">PubMed</a>]</span></li>
<li id="R2"><span class='au'>Palmer, D. B.</span>: <span class="ti">The effect of age on thymic function.</span> <span class='so'>Front. Immunol., 4, 316 (2013)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/24109481" target="_blank">PubMed</a>]</span></li>
<li id="R3"><span class='au'>Dooley, J. & Liston, A.</span>: <span class="ti">Molecular control over thymic involution: from cytokines and microRNA to aging and adipose tissue.</span> <span class='so'>Eur. J. Immunol., 42, 1073-1079 (2012)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/22539280" target="_blank">PubMed</a>]</span></li>
<li id="R4"><span class='au'>Chaudhry, M. S., Velardi, E., Malard, F. et al.</span>: <span class="ti">Immune reconstitution after allogeneic hematopoietic stem cell transplantation: time to T up the thymus.</span> <span class='so'>J. Immunol., 198, 40-46 (2017)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/27994167" target="_blank">PubMed</a>]</span></li>
<li id="R5"><span class='au'>Hamazaki, Y., Sekai, M. & Minato, N.</span>: <span class="ti">Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution.</span> <span class='so'>Immunol. Rev., 271, 38-55 (2016)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/27088906" target="_blank">PubMed</a>]</span></li>
<li id="R6"><span class='au'>Hamazaki, Y.</span>: <span class="ti">Adult thymic epithelial cell (TEC) progenitors and TEC stem cells: models and mechanisms for TEC development and maintenance.</span> <span class='so'>Eur. J. Immunol., 45, 2985-2993 (2015)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/26362014" target="_blank">PubMed</a>]</span></li>
<li id="R7"><span class='au'>Hamazaki, Y., Fujita, H., Kobayashi, T. et al.</span>: <span class="ti">Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin.</span> <span class='so'>Nat. Immunol., 8, 304-311 (2007)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/17277780" target="_blank">PubMed</a>]</span></li>
<li id="R8"><span class='au'>Sekai, M., Hamazaki, Y. & Minato, N.</span>: <span class="ti">Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance.</span> <span class='so'>Immunity, 41, 753-761 (2014)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25464854" target="_blank">PubMed</a>] [<a href="http://first.lifesciencedb.jp/archives/9645" target="_blank">V_r[</a>]</span></li>
<li id="R9"><span class='au'>Goronzy, J. J., Li, G., Yang, Z. et al.</span>: <span class="ti">The janus head of T cell aging: autoimmunity and immunodeficiency.</span> <span class='so'>Front. Immunol., 4, 131 (2013)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/23761790" target="_blank">PubMed</a>]</span></li>
<li id="R10"><span class='au'>Jackson, M. L., Nelson, J. C., Weiss, N. S. et al.</span>: <span class="ti">Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study.</span> <span class='so'>Lancet, 372, 398-405 (2008)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/18675690" target="_blank">PubMed</a>]</span></li>
<li id="R11"><span class='au'>Goronzy, J. J. & Weyand, C. M.</span>: <span class="ti">Understanding immunosenescence to improve responses to vaccines.</span> <span class='so'>Nat. Immunol., 14, 428-436 (2013)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/23598398" target="_blank">PubMed</a>]</span></li>
<li id="R12"><span class='au'>Medzhitov, R.</span>: <span class="ti">Origin and physiological roles of inflammation.</span> <span class='so'>Nature, 454, 428-435 (2008)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/18650913" target="_blank">PubMed</a>]</span></li>
<li id="R13"><span class='au'>Cooper, G. S. & Stroehla, B. C.</span>: <span class="ti">The epidemiology of autoimmune diseases.</span> <span class='so'>Autoimmun. Rev., 2, 119-125 (2003)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/12848952" target="_blank">PubMed</a>]</span></li>
<li id="R14"><span class='au'>Li, G., Yu, M., Lee, W. W. et al.</span>: <span class="ti">Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity.</span> <span class='so'>Nat. Med., 18, 1518-1524 (2012)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/23023500" target="_blank">PubMed</a>]</span></li>
<li id="R15"><span class='au'>den Braber, I., Mugwagwa, T., Vrisekoop, N. et al.</span>: <span class="ti">Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans.</span> <span class='so'>Immunity, 36, 288-297 (2012)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/22365666" target="_blank">PubMed</a>]</span></li>
<li id="R16"><span class='au'>Sauce, D., Larsen, M., Fastenackels, S. et al.</span>: <span class="ti">Evidence of premature immune aging in patients thymectomized during early childhood.</span> <span class='so'>J. Clin. Invest., 119, 3070-3078 (2009)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/19770514" target="_blank">PubMed</a>]</span></li>
<li id="R17"><span class='au'>Appay, V., Sauce, D. & Prelog, M.</span>: <span class="ti">The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals.</span> <span class='so'>Aging, 2, 78-81 (2010)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/20354268" target="_blank">PubMed</a>]</span></li>
<li id="R18"><span class='au'>van Gent, R., Schadenberg, A. W., Otto, S. A. et al.</span>: <span class="ti">Long-term restoration of the human T-cell compartment after thymectomy during infancy: a role for thymic regeneration?</span> <span class='so'>Blood, 118, 627-634 (2011)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/21628415" target="_blank">PubMed</a>]</span></li>
<li id="R19"><span class='au'>Dowling, M. R. & Hodgkin, P. D.</span>: <span class="ti">Why does the thymus involute? A selection-based hypothesis.</span> <span class='so'>Trends Immunol., 30, 295-300 (2009)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/19540805" target="_blank">PubMed</a>]</span></li>
<li id="R20"><span class='au'>Baccala, R. & Theofilopoulos, A. N.</span>: <span class="ti">The new paradigm of T-cell homeostatic proliferation-induced autoimmunity.</span> <span class='so'>Trends Immunol., 26, 5-8 (2005)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/15629402" target="_blank">PubMed</a>]</span></li>
<li id="R21"><span class='au'>Goronzy, J. J. & Weyand, C. M.</span>: <span class="ti">Immune aging and autoimmunity.</span> <span class='so'>Cell. Mol. Life Sci., 69, 1615-1623 (2012)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/22466672" target="_blank">PubMed</a>]</span></li>
<li id="R22"><span class='au'>Sprent, J. & Surh, C. D.</span>: <span class="ti">Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells.</span> <span class='so'>Nat. Immunol., 12, 478-484 (2011)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/21739670" target="_blank">PubMed</a>]</span></li>
<li id="R23"><span class='au'>Van Kaer, L.</span>: <span class="ti">Innate and virtual memory T cells in man.</span> <span class='so'>Eur. J. Immunol., 45, 1916-1920 (2015)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/26013879" target="_blank">PubMed</a>]</span></li>
<li id="R24"><span class='au'>Nikolich-Zugich, J.</span>: <span class="ti">Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories.</span> <span class='so'>J. Immunol., 193, 2622-2629 (2014)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25193936" target="_blank">PubMed</a>]</span></li>
<li id="R25"><span class='au'>Lages, C. S., Suffia, I., Velilla, P. A. et al.</span>: <span class="ti">Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation.</span> <span class='so'>J. Immunol., 181, 1835-1848 (2008)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/18641321" target="_blank">PubMed</a>]</span></li>
<li id="R26"><span class='au'>Shimatani, K., Nakashima, Y., Hattori, M. et al.</span>: <span class="ti">PD-1<sup>+</sup> memory phenotype CD4<sup>+</sup> T cells expressing C/EBP underlie T cell immunodepression in senescence and leukemia.</span> <span class='so'>Proc. Natl. Acad. Sci. USA, 106, 15807-15812 (2009)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/19805226" target="_blank">PubMed</a>]</span></li>
<li id="R27"><span class='au'>Tahir, S., Fukushima, Y., Sakamoto, K. et al.</span>: <span class="ti">A CD153<sup>+</sup>CD4<sup>+</sup> T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production.</span> <span class='so'>J. Immunol., 194, 5725-5735 (2015)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25972477" target="_blank">PubMed</a>]</span></li>
<li id="R28"><span class='au'>Sakamoto, K., Fukushima, Y., Ito, K. et al.</span>: <span class="ti">Osteopontin in spontaneous germinal centers inhibits apoptotic cell engulfment and promotes anti-nuclear antibody production in lupus-prone mice.</span> <span class='so'>J. Immunol., 197, 2177-2186 (2016)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/27534552" target="_blank">PubMed</a>]</span></li>
<li id="R29"><span class='au'>Kuwahara, M., Suzuki, J., Tofukuji, S. et al.</span>: <span class="ti">The Menin-Bach2 axis is critical for regulating CD4 T-cell senescence and cytokine homeostasis.</span> <span class='so'>Nat. Commun., 5, 3555 (2014)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/24694524" target="_blank">PubMed</a>]</span></li>
<li id="R30"><span class='au'>Sato, K., Kato, A., Sekai, M. et al.</span>: <span class="ti">Physiologic thymic involution underlies age-dependent accumulation of senescence-associated CD4<sup>+</sup> T cells.</span> <span class='so'>J. Immunol., 199, 138-148 (2017)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/28539430" target="_blank">PubMed</a>]</span></li>
<li id="R31"><span class='au'>Shirakawa, K., Yan, X., Shinmura, K. et al.</span>: <span class="ti">Obesity accelerates T cell senescence in murine visceral adipose tissue.</span> <span class='so'>J. Clin. Invest., 126, 4626-4639 (2016)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/27820698" target="_blank">PubMed</a>]</span></li>
<li id="R32"><span class='au'>Kato, A., Takaori-Kondo, A., Minato, N. et al.</span>: <span class="ti">Generation of CXCR3<sup>high</sup> naive phenotype CD8<sup>+</sup> T cells with high capacity of interferon- production during homeostatic T-cell proliferation.</span> <span class='so'>Eur. J. Immunol., <em>in press</em>[<a href="http://www.ncbi.nlm.nih.gov/pubmed/xxx" target="_blank">PubMed</a>]</span></li>
<li id="R33"><span class='au'>Akbar, A. N. & Henson, S. M.</span>: <span class="ti">Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?</span> <span class='so'>Nat. Rev. Immunol., 11, 289-295 (2011)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/21436838" target="_blank">PubMed</a>]</span></li>
<li id="R34"><span class='au'>Akbar, A. N., Henson, S. M. & Lanna, A.</span>: <span class="ti">Senescence of T lymphocytes: implications for enhancing human immunity.</span> <span class='so'>Trends Immunol., 37, 866-876 (2016)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/27720177" target="_blank">PubMed</a>]</span></li>
<li id="R35"><span class='au'>Schurich, A. & Henson, S. M.</span>: <span class="ti">The many unknowns concerning the bioenergetics of exhaustion and senescence during chronic viral infection.</span> <span class='so'>Front. Immunol., 5, 468 (2014)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25309548" target="_blank">PubMed</a>]</span></li>
<li id="R36"><span class='au'>Nikolich-Zugich, J.</span>: <span class="ti">Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.</span> <span class='so'>Nat. Rev. Immunol., 8, 512-522 (2008)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/18469829" target="_blank">PubMed</a>]</span></li>
<li id="R37"><span class='au'>Lanna, A., Henson, S. M., Escors, D. et al.</span>: <span class="ti">The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells.</span> <span class='so'>Nat. Immunol., 15, 965-972 (2014)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25151490" target="_blank">PubMed</a>]</span></li>
<li id="R38"><span class='au'>Di Mitri, D., Azevedo, R. I., Henson, S. M. et al.</span>: <span class="ti">Reversible senescence in human CD4<sup>+</sup>CD45RA<sup>+</sup>CD27<sup>-</sup> memory T cells.</span> <span class='so'>J. Immunol., 187, 2093-2100 (2011)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/21788446" target="_blank">PubMed</a>]</span></li>
<li id="R39"><span class='au'>Henson, S. M., Macaulay, R., Riddell, N. E. et al.</span>: <span class="ti">Blockade of PD-1 or p38 MAP kinase signaling enhances senescent human CD8<sup>+</sup> T-cell proliferation by distinct pathways.</span> <span class='so'>Eur. J. Immunol., 45, 1441-1451 (2015)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25707450" target="_blank">PubMed</a>]</span></li>
<li id="R40"><span class='au'>Lanna, A., Gomes, D. C., Muller-Durovic, B. et al.</span>: <span class="ti">A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging.</span> <span class='so'>Nat. Immunol., 18, 354-363 (2017)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/28114291" target="_blank">PubMed</a>]</span></li>
<li id="R41"><span class='au'>Furman, D., Jojic, V., Sharma, S. et al.</span>: <span class="ti">Cytomegalovirus infection enhances the immune response to influenza.</span> <span class='so'>Sci. Transl. Med., 7, 281ra243 (2015)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25834109" target="_blank">PubMed</a>]</span></li>
<li id="R42"><span class='au'>Mannick, J. B., Del Giudice, G., Lattanzi, M. et al.</span>: <span class="ti">mTOR inhibition improves immune function in the elderly.</span> <span class='so'>Sci. Transl. Med., 6, 268ra179 (2014)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/25540326" target="_blank">PubMed</a>]</span></li>
</ol>
<div class="au-profile">
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<span class="author">M mqiYoko Hamazakij</span>
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URLF<a href="http://www.cira.kyoto-u.ac.jp/hmy/" target="_blank">http://www.cira.kyoto-u.ac.jp/hmy/</a>

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? 2018 MmqE  Licensed under <a href="http://creativecommons.org/licenses/by/2.1/jp/" target="_blank">CC \ 2.1 {</a>
