Redefining thymus medulla specialization for central tolerance.
Redefining thymus medulla specialization for central tolerance.
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DOI：
10.1084/jem.20171000
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发表时间：
2017-11-06
期刊：
影响因子：
--
通讯作者：
Anderson G
中科院分区：
文献类型：
--
作者：
Cosway EJ;Lucas B;James KD;Parnell SM;Carvalho-Gaspar M;White AJ;Tumanov AV;Jenkinson WE;Anderson G
胸腺髓质通过中枢耐受防止T细胞驱动的自身免疫。Cosway等人表明，这种特化独立于经典定义其结构的拓扑结构发生，并证明髓质功能需要LTβ R介导的树突状细胞负选择调节。在αβT细胞发育过程中，胸腺髓质是T细胞耐受的重要微环境。这种功能特化归因于其典型的有组织拓扑结构，该拓扑结构由包含髓质胸腺上皮细胞（mTEC）网络的分支结构组成，以支持阴性选择和Foxp 3 + T调节细胞（T-reg）发育。在这里，通过对胸腺髓质调节因子β-光敏素β受体（LTβR）进行TEC特异性缺失，我们表明胸腺耐受机制的运作独立于LTβ R介导的mTEC发育和组织。与此一致，mTEC继续表达Fezf 2和Aire，胸腺内自身抗原的调节因子，并支持T-reg发育，尽管LTβ R介导的髓质器官发生丧失。此外，我们证明LTβR通过调节有效的胸腺细胞负选择所需的胸腺内树突状细胞（DC）的频率和组成来控制胸腺耐受。总之，我们的研究表明，胸腺耐受的胸腺髓质特化与髓质器官发生分离，而是涉及LTβ R介导的胸腺DC库的调节。
The thymus medulla prevents T cell–driven autoimmunity via central tolerance. Cosway et al. show that this specialization occurs independently of the topology that classically defines its structure and demonstrate that medulla function requires LTβR-mediated regulation of dendritic cells for negative selection. During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3+ T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin β receptor (LTβR), we show that thymic tolerance mechanisms operate independently of LTβR-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LTβR-mediated medulla organogenesis. Moreover, we demonstrate that LTβR controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LTβR-mediated regulation of the thymic DC pool.
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DOI：
10.1084/jem.20070795
发表时间：
2007-10-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gray D;Abramson J;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
32.4
作者：
Ehrlich, Lauren I. Richie;Oh, David Y.;Lewis, Richard S.
通讯作者：
Lewis, Richard S.
影响因子：
64.8
作者：
Daniels, Mark A.;Teixeiro, Emma;Palmer, Ed
通讯作者：
Palmer, Ed
影响因子：
30.5
作者：
Aschenbrenner, Katharina;D'Cruz, Louise M.;Klein, Ludger
通讯作者：
Klein, Ludger
影响因子：
56.9
作者：
Anderson, MS;Venanzi, ES;Mathis, D
通讯作者：
Mathis, D