Extrathymically generated regulatory T cells control mucosal TH2 inflammation.
Extrathymically generated regulatory T cells control mucosal TH2 inflammation.
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DOI：
10.1038/nature10772
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发表时间：
2012-02-08
期刊：
影响因子：
64.8
通讯作者：
Rudensky, Alexander Y.
中科院分区：
文献类型：
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作者：
Josefowicz, Steven Z.;Niec, Rachel E.;Kim, Hye Young;Treuting, Piper;Chinen, Takatoshi;Zheng, Ye;Umetsu, Dale T.;Rudensky, Alexander Y.
粘膜界面处促炎和抗炎机制之间的平衡，即组成性暴露于微生物和非微生物外来物质的部位，允许有效地保护免受病原体的侵害，同时防止与过敏、哮喘和肠道炎症相关的不良炎症反应。调节性T（Treg）细胞防止粘膜界面处的全身性和组织特异性自身免疫和炎性病变。这些细胞在胸腺（tTreg细胞）和外周（iTreg细胞）中产生，并且它们的双重来源意味着在免疫稳态中tTreg和iTreg细胞之间的分工。在这里，我们证明了iTreg细胞分化的高度选择性阻断不会导致无端的多器官自身免疫，诱导的组织特异性自身免疫病理学（EAE）的恶化，或促炎性Th1和Th17细胞反应的增加。然而，iTreg细胞缺陷小鼠在胃肠道和肺的粘膜部位自发地发展出明显的Th2型病理，具有过敏性炎症和哮喘的标志。此外，iTreg细胞缺乏改变了肠道微生物群落。这些结果表明，尽管胸腺中产生的Treg细胞似乎足以控制全身性和组织特异性自身免疫，但Treg细胞的胸腺外分化影响了肠道微生物群组成，并在抑制粘膜界面处的过敏型炎症中发挥了独特的基本功能。
A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma, and intestinal inflammation. Regulatory T (Treg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tTreg cells) and in the periphery (iTreg cells) and their dual origin implies a division of labor between tTreg and iTreg cells in immune homeostasis. Here we demonstrate that a highly selective blockage in differentiation of iTreg cells did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology (EAE), or increased pro-inflammatory Th1 and Th17 cell responses. However, iTreg cell-deficient mice spontaneously developed pronounced Th2 type pathologies at mucosal sites — in the gastrointestinal tract and lungs — with hallmarks of allergic inflammation and asthma. Furthermore, iTreg cell deficiency altered gut microbial communities. These results suggest that whereas Treg cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of Treg cells impacts commensal microbiota composition and serves a distinct, essential function in restraint of allergic type inflammation at mucosal interfaces.
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影响因子：
4.4
作者：
Schloss, Patrick D.;Westcott, Sarah L.;Weber, Carolyn F.
通讯作者：
Weber, Carolyn F.
影响因子：
32.4
作者：
Hill JA;Hall JA;Sun CM;Cai Q;Ghyselinck N;Chambon P;Belkaid Y;Mathis D;Benoist C
通讯作者：
Benoist C
DOI：
10.1073/pnas.0811556106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Komatsu, Noriko;Mariotti-Ferrandiz, Maria Encarnita;Hori, Shohei
通讯作者：
Hori, Shohei
DOI：
10.1084/jem.20030152
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen W;Jin W;Hardegen N;Lei KJ;Li L;Marinos N;McGrady G;Wahl SM
通讯作者：
Wahl SM
影响因子：
30.5
作者：
通讯作者：
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