Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea.
J Exp Med. 2021 Apr 5;218(4). doi: 10.1084/jem.20201665.
Conventional CD4+ T cells are differentiated into CD4+CD8αα+ intraepithelial lymphocytes (IELs) in the intestine; however, the roles of intestinal epithelial cells (IECs) are poorly understood. Here, we showed that IECs expressed MHC class II (MHC II) and programmed death-ligand 1 (PD-L1) induced by the microbiota and IFN-γ in the distal part of the small intestine, where CD4+ T cells were transformed into CD4+CD8αα+ IELs. Therefore, IEC-specific deletion of MHC II and PD-L1 hindered the development of CD4+CD8αα+ IELs. Intracellularly, PD-1 signals supported the acquisition of CD8αα by down-regulating the CD4-lineage transcription factor, T helper-inducing POZ/Krüppel-like factor (ThPOK), via the Src homology 2 domain-containing tyrosine phosphatase (SHP) pathway. Our results demonstrate that noncanonical antigen presentation with cosignals from IECs constitutes niche adaptation signals to develop tissue-resident CD4+CD8αα+ IELs.
常规的 CD4+T 细胞在肠道中分化为 CD4+CD8αα+上皮内淋巴细胞（IEL）；然而，肠上皮细胞（IEC）的作用仍知之甚少。在这里，我们表明，IEC 在小肠远端表达 MHC Ⅱ类（MHC II）和程序性死亡配体 1（PD-L1），由微生物群和 IFN-γ诱导，在该处 CD4+T 细胞转化为 CD4+CD8αα+IEL。因此，IEC 特异性缺失 MHC II 和 PD-L1 阻碍了 CD4+CD8αα+IEL 的发育。在细胞内，PD-1 信号通过 Src 同源 2 结构域包含的酪氨酸磷酸酶（SHP）途径下调辅助诱导 POZ/Krüppel 样因子（ThPOK）的 CD4 谱系转录因子，支持 CD8αα 的获得。我们的结果表明，来自 IEC 的非经典抗原呈递与共刺激信号构成了适应组织驻留 CD4+CD8αα+IEL 发育的生态位适应信号。
