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Blood:维甲酸反应性CD8效应T细胞在胃肠GvHD富含IL-23的组织中选择性扩增

2020-09-22 MedSci原创 MedSci原创

维甲酸主要增加同种异体反应性的RARahi CD8效应T细胞,包括体内鉴定的表型细胞。IL-23可通过选择性增加CD8效应T细胞上b7整合素的表达和降低具有调节细胞表型的CD4 T细胞来加强这一效应。

胃肠道(GI)移植物抗宿主病(GvHD)是异基因造血干细胞移植(AHST)的主要障碍。代谢产物维甲酸(RA)通过表达RA受体α(RARα)的同种反应性T细胞增强小鼠的GI-GvHD,但RA反应性细胞在人GI-GvHD中的作用尚不清楚。

在本研究中,Ball等使用传统的和新型序贯免疫染色和流式细胞术来仔细观察AHST患者组织和血液中的RA反应性T细胞,并表征RA对人类T细胞同种异体反应的影响。

(在GI-GvHD组织中,RARαhi单核细胞数量增多)

在RA暴露后,人单个核细胞RARα的表达水平增加。在GI-GvHD组织中,RARαhi单核细胞数量增多,这些细胞内的RA结合蛋白增多,定位于组织损伤的地方,与GvHD的严重程度和病死率相关。

(在GvHD组织中,T-bet的表达增多)

通过靶向候选蛋白方法,研究人员预测了在微环境IL-23增加的情况下RA反应性T细胞的表型。序贯免疫染色证实了存在一群具有预测表型的RARahi CD8T细胞,共表达效应T细胞转录因子T-bet和IL-23特异性受体。这些细胞在GI-GvHD组织中增加,但在皮肤-GvHD组织中没有增加,并且在GI-GvHD患者的血液中有选择性地扩增。

最后,功能研究显示,RA主要增加同种异体反应性的RARahi CD8效应T细胞,包括体内鉴定的表型细胞。富含IL-23的条件可通过选择性增加CD8效应T细胞上b7整合素的表达和降低具有调节细胞表型的CD4 T细胞来加强这一效应。

总之,Ball等鉴定出了一组具有独特表型的RA反应性效应T细胞,它们在人GI-GvHD中选择性扩增,可作为潜在的新的治疗靶点。

原始出处:

Ball Jennifer A,Clear Andrew James,Aries James et al. Retinoic acid-responsive CD8 effector T-cells are selectively increased in IL-23-rich tissue in gastrointestinal GvHD. Blood, Sep 09 2020.

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    2020-10-14 12513136m76(暂无昵称)

    学习了很不错,每天都要来学习一下

    0

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  5. [GetPortalCommentsPageByObjectIdResponse(id=2022850, encodeId=2f7d202285010, content=<a href='/topic/show?id=188b3e7309c' target=_blank style='color:#2F92EE;'>#反应性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37730, encryptionId=188b3e7309c, topicName=反应性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d7532500500, createdName=12499e01m47暂无昵称, createdTime=Fri Oct 02 20:42:37 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1922966, encodeId=2e0d1922966a1, content=<a href='/topic/show?id=78f794e800a' target=_blank style='color:#2F92EE;'>#选择性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94780, encryptionId=78f794e800a, topicName=选择性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0802500050, createdName=肉我只吃一口, createdTime=Thu Aug 12 06:42:37 CST 2021, time=2021-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=892089, encodeId=928a8920890e, content=学习了很不错,每天都要来学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201211/3bfec5fbc20b4196abdf11d80e7de414/8f53131a3a5e4e5caab63204a79128f2.jpg, createdBy=90402537000, createdName=12513136m76(暂无昵称), createdTime=Wed Oct 14 19:49:26 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479664, encodeId=955c14e9664af, content=<a href='/topic/show?id=6e0e9655fd' target=_blank style='color:#2F92EE;'>#IL-23#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9655, encryptionId=6e0e9655fd, topicName=IL-23)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e8f7562522, createdName=124987a0m68(暂无昵称), createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605406, encodeId=075716054065e, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626068, encodeId=bd71162606874, content=<a href='/topic/show?id=87369652f3' target=_blank style='color:#2F92EE;'>#IL-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9652, encryptionId=87369652f3, topicName=IL-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea8220955712, createdName=tomyang93, createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=887436, encodeId=43e688e4366c, content=学到了, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80552210375, createdName=女医生, createdTime=Tue Sep 22 18:30:10 CST 2020, time=2020-09-22, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2022850, encodeId=2f7d202285010, content=<a href='/topic/show?id=188b3e7309c' target=_blank style='color:#2F92EE;'>#反应性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37730, encryptionId=188b3e7309c, topicName=反应性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d7532500500, createdName=12499e01m47暂无昵称, createdTime=Fri Oct 02 20:42:37 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1922966, encodeId=2e0d1922966a1, content=<a href='/topic/show?id=78f794e800a' target=_blank style='color:#2F92EE;'>#选择性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94780, encryptionId=78f794e800a, topicName=选择性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0802500050, createdName=肉我只吃一口, createdTime=Thu Aug 12 06:42:37 CST 2021, time=2021-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=892089, encodeId=928a8920890e, content=学习了很不错,每天都要来学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201211/3bfec5fbc20b4196abdf11d80e7de414/8f53131a3a5e4e5caab63204a79128f2.jpg, createdBy=90402537000, createdName=12513136m76(暂无昵称), createdTime=Wed Oct 14 19:49:26 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479664, encodeId=955c14e9664af, content=<a href='/topic/show?id=6e0e9655fd' target=_blank style='color:#2F92EE;'>#IL-23#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9655, encryptionId=6e0e9655fd, topicName=IL-23)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e8f7562522, createdName=124987a0m68(暂无昵称), createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605406, encodeId=075716054065e, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626068, encodeId=bd71162606874, content=<a href='/topic/show?id=87369652f3' target=_blank style='color:#2F92EE;'>#IL-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9652, encryptionId=87369652f3, topicName=IL-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea8220955712, createdName=tomyang93, createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=887436, encodeId=43e688e4366c, content=学到了, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80552210375, createdName=女医生, createdTime=Tue Sep 22 18:30:10 CST 2020, time=2020-09-22, status=1, ipAttribution=)]
    2020-09-24 tomyang93
  7. [GetPortalCommentsPageByObjectIdResponse(id=2022850, encodeId=2f7d202285010, content=<a href='/topic/show?id=188b3e7309c' target=_blank style='color:#2F92EE;'>#反应性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37730, encryptionId=188b3e7309c, topicName=反应性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d7532500500, createdName=12499e01m47暂无昵称, createdTime=Fri Oct 02 20:42:37 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1922966, encodeId=2e0d1922966a1, content=<a href='/topic/show?id=78f794e800a' target=_blank style='color:#2F92EE;'>#选择性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94780, encryptionId=78f794e800a, topicName=选择性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a0802500050, createdName=肉我只吃一口, createdTime=Thu Aug 12 06:42:37 CST 2021, time=2021-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=892089, encodeId=928a8920890e, content=学习了很不错,每天都要来学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201211/3bfec5fbc20b4196abdf11d80e7de414/8f53131a3a5e4e5caab63204a79128f2.jpg, createdBy=90402537000, createdName=12513136m76(暂无昵称), createdTime=Wed Oct 14 19:49:26 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1479664, encodeId=955c14e9664af, content=<a href='/topic/show?id=6e0e9655fd' target=_blank style='color:#2F92EE;'>#IL-23#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9655, encryptionId=6e0e9655fd, topicName=IL-23)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e8f7562522, createdName=124987a0m68(暂无昵称), createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605406, encodeId=075716054065e, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1626068, encodeId=bd71162606874, content=<a href='/topic/show?id=87369652f3' target=_blank style='color:#2F92EE;'>#IL-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9652, encryptionId=87369652f3, topicName=IL-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ea8220955712, createdName=tomyang93, createdTime=Thu Sep 24 05:42:37 CST 2020, time=2020-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=887436, encodeId=43e688e4366c, content=学到了, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80552210375, createdName=女医生, createdTime=Tue Sep 22 18:30:10 CST 2020, time=2020-09-22, status=1, ipAttribution=)]
    2020-09-22 女医生

    学到了

    0

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