Peripheral education of the immune system by colonic commensal microbiota.
Peripheral education of the immune system by colonic commensal microbiota.
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DOI：
10.1038/nature10434
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发表时间：
2011-09-21
期刊：
影响因子：
64.8
通讯作者：
Hsieh, Chyi-Song
中科院分区：
文献类型：
--
作者：
Lathrop, Stephanie K.;Bloom, Seth M.;Rao, Sindhuja M.;Nutsch, Katherine;Lio, Chan-Wang;Santacruz, Nicole;Peterson, Daniel A.;Stappenbeck, Thaddeus S.;Hsieh, Chyi-Song
免疫系统对自身的耐受，从而防止自身免疫的指令，是通过在一个专门的器官-胸腺中培养T细胞来促进的，在胸腺中，自我反应细胞被消除或分化为耐受的Foxp3+调节性T(Treg)细胞。然而，目前尚不清楚T细胞是否也被培养成对外来抗原的耐受性，例如来自共生细菌的抗原，以预防炎症性肠病等免疫病理。在这里，我们表明，与共生微生物群的接触导致Treg细胞的外围产生，而不是致病效应器。我们观察到，结肠Treg细胞利用与其他部位Treg细胞不同的T细胞抗原受体(TCR)，这意味着局部抗原在塑造结肠Treg细胞群体中起着重要作用。基于普通结肠Treg TCR的体外反应性，许多局部抗原似乎来自共生菌。有趣的是，这些TCR并没有促进胸腺Treg细胞的发育，这意味着许多结肠Treg细胞是通过抗原驱动的外周Treg细胞发育而产生的。通过创建逆转录病毒骨髓嵌合体和TCR转基因线虫对其中两个TCR进行进一步分析，结果表明，我们的小鼠群体特有的微生物群需要从其他原始T细胞生成结肠Treg细胞。过继转移研究证明，如果表达这些TCR的T细胞不能经过Treg细胞的发育而成为效应细胞，它们就有可能诱发结肠炎。这些结果表明，对个体微生物区系做出反应的抗原特异性Treg细胞群体的有效外周生成提供了重要的胸腺后免疫系统对外来抗原的教育，从而提供了对共生微生物区系的耐受性。
The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, where self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3+ regulatory T(Treg) cells. However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, in order to prevent immunopathology such as inflammatory bowel disease. Here, we show that encounter with commensal microbiota results in the peripheral generation of Treg cells, rather than pathogenic effectors. We observed that colonic Treg cells utilized T cell antigen receptors (TCRs)different from those used by Treg cells in other locations, implying an important role for local antigens in shaping the colonic Treg cell population. Many of the local antigens appeared to be derived from commensal bacteria based on the in vitro reactivity of common colon Treg TCRs. Interestingly, these TCRs did not facilitate thymic Treg cell development, implying that manycolonic Treg cells arise instead via antigen-driven peripheral Treg cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimeras and a TCR transgenic linerevealed that microbiota indigenous to our mouse colony was required for the generation of colonic Treg cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo Treg cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of Treg cells in response to an individual’s microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
DOI：
10.1084/jem.20081359
发表时间：
2008-12-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lathrop SK;Santacruz NA;Pham D;Luo J;Hsieh CS
通讯作者：
Hsieh CS
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA