Niche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation

Sookjin Moon, Yunji Park, Sumin Hyeon, Young Min Kim, Ji Hae Kim, Hyekang Kim, Subin Park, Kun Joo Lee, Bon Kyoung Koo, Sang Jun Ha, Seung Woo Lee

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16 Citations (Scopus)


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.

Original languageEnglish
Article number20201665
JournalJournal of Experimental Medicine
Issue number4
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 Moon et al.

All Science Journal Classification (ASJC) codes

  • General Medicine


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