Open AccessNiche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation
Author(s) -
Seokbae Moon,
Yunji Park,
Sumin Hyeon,
YoungMin Kim,
Ji-Hae Kim,
Hyekang Kim,
Subin Park,
Kun-Joo Lee,
Bon–Kyoung Koo,
SangJun Ha,
Seung-Woo Lee
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20201665
Subject(s) - intraepithelial lymphocyte , biology , cd8 , mhc class i , microbiology and biotechnology , major histocompatibility complex , protein tyrosine phosphatase , mhc class ii , immunology , antigen , immune system , signal transduction
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.