Diabetes Center, University of California, San Francisco, San Francisco, CA 94143-0540, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143-0540, USA.
Immunity. 2013 Sep 19;39(3):560-72. doi: 10.1016/j.immuni.2013.08.005. Epub 2013 Aug 29.
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), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) 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.
自身免疫调节因子 (Aire) 对于预防自身免疫至关重要；其在胸腺中的作用最为明显，通过组织特异性抗原 (TSA) 表达促进自身耐受。最近，在鼠类次级淋巴器官中描述了胸腺外表达 Aire 的细胞 (eTACs)，但这些细胞的特性及其在免疫耐受中的作用仍不清楚。在这里，我们表明 eTACs 是一个离散的主要组织相容性复合体 II (MHC II)(hi)、CD80(lo)、CD86(lo)、上皮细胞黏附分子 (EpCAM)(hi)、CD45(lo) 的骨髓来源的外周抗原呈递细胞 (APC) 群体。我们还证明，eTACs 可以通过一种不依赖调节性 T 细胞 (Treg) 的机制来有效地使 CD4 ⁺ T 细胞失活，并且对先天炎症刺激具有抗性。这些发现共同进一步将 eTACs 定义为次级淋巴器官中独特的耐受性细胞群体。
