Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4⁺ T cells.

Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4⁺ T cells.
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DOI:
10.1016/j.immuni.2013.08.005
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发表时间:
2013-09-19
期刊:
影响因子:
32.4
通讯作者:
Anderson MS
Anderson MS
中科院分区:
医学1区
文献类型:
--
作者:
Gardner JM;Metzger TC;McMahon EJ;Au-Yeung BB;Krawisz AK;Lu W;Price JD;Johannes KP;Satpathy AT;Murphy KM;Tarbell KV;Weiss A;Anderson MS

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自身免疫调节因子(AIRE)对于预防自身免疫是必不可少的;其作用在胸腺中最好理解,在胸腺中其通过组织特异性抗原(TSA)表达促进自身耐受。最近,胸腺外Aire表达细胞(eTAC)已被描述在小鼠次级淋巴器官,但这种细胞的身份和它们在免疫耐受中的作用仍然不清楚。在这里,我们已经表明,eTAC是一个离散的主要组织相容性复合物II类(MHC II)hi,CD 80 lo,CD 86 lo,上皮细胞粘附分子(EpCAM)hi,CD 45 lo骨髓来源的外周抗原呈递细胞(APC)的人口。我们还证明了eTAC可以通过一种不需要调节性T细胞(Treg)的机制在功能上抑制CD 4 + T细胞,并且对先天性炎症刺激具有抗性。这些发现进一步将eTAC定义为次级淋巴器官中的独特致耐受性细胞群。
The autoimmune regulator (AIRE) is essential for prevention of autoimmunity; its role is best understood in the thymus where it promotes self-tolerance through tissue-specific antigen (TSA) expression. Recently, extrathymic Aire-expressing cells (eTACs) have been described in murine secondary lymphoid organs, but the identity of such cells and their role in immune tolerance remains unclear. Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)hi, CD80lo, CD86lo, epithelial cell adhesion molecule (EpCAM)hi, CD45lo bone marrow-derived peripheral antigen presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4+ T cells through a mechanism that does not require regulatory T cells (Treg), and is resistant to innate inflammatory stimuli. Together these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.
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