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.
|Journal||Journal of Experimental Medicine|
|Publication status||Published - 2021|
Bibliographical noteFunding Information:
This work was supported by National Research Foundation of Korea grants funded by the Korean government (MSIT; NRF-2017R1A5A1015366, NRF-2017R1A2B4005400, and NRF-2020R1A2C1100997) and the BK21 Program funded by the Ministry of Education, Korea (4120200313623).
© 2021 Moon et al.
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