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.
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January 28 2021
Niche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation
Sookjin Moon
,
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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Yunji Park
,
Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
2
POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
Yunji Park: yunji@postech.ac.kr
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Sumin Hyeon
,
Sumin Hyeon
Investigation, Methodology, Resources, Validation
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Young-Min Kim
,
Young-Min Kim
Investigation, Writing - review & editing
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Ji-Hae Kim
,
Ji-Hae Kim
Investigation, Writing - original draft
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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Hyekang Kim
,
Hyekang Kim
Methodology, Writing - review & editing
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
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Subin Park
,
Subin Park
Data curation, Investigation, Methodology
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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Kun-Joo Lee
,
Kun-Joo Lee
Formal analysis, Visualization
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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Bon-Kyoung Koo
,
Bon-Kyoung Koo
Conceptualization, Data curation, Supervision, Writing - review & editing
4
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria
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Sang-Jun Ha
,
Sang-Jun Ha
Resources, Writing - review & editing
5
Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Republic of Korea
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Seung-Woo Lee
Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Validation, Writing - original draft, Writing - review & editing
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
Correspondence to Seung-Woo Lee: sw_lee@postech.ac.kr
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Sookjin Moon
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
Yunji Park
Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
2
POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
Sumin Hyeon
Investigation, Methodology, Resources, Validation
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
Young-Min Kim
Investigation, Writing - review & editing
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
Ji-Hae Kim
Investigation, Writing - original draft
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
Hyekang Kim
Methodology, Writing - review & editing
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
Subin Park
Data curation, Investigation, Methodology
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
Kun-Joo Lee
Formal analysis, Visualization
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
Bon-Kyoung Koo
Conceptualization, Data curation, Supervision, Writing - review & editing
4
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria
Sang-Jun Ha
Resources, Writing - review & editing
5
Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Republic of Korea
Seung-Woo Lee
Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Validation, Writing - original draft, Writing - review & editing
1
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
3
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea
*
S. Moon and Y. Park contributed equally to this paper.
Yunji Park: yunji@postech.ac.kr
Correspondence to Seung-Woo Lee: sw_lee@postech.ac.kr
Received:
August 05 2020
Revision Received:
November 12 2020
Accepted:
December 18 2020
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding:
National Research Foundation of Korea
(NRF-2017R1A5A1015366, NRF-2017R1A2B4005400, NRF-2020R1A2C1100997)
© 2021 Moon et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2021) 218 (4): e20201665.
Article history
Received:
August 05 2020
Revision Received:
November 12 2020
Accepted:
December 18 2020
Citation
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; Niche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation. J Exp Med 5 April 2021; 218 (4): e20201665. doi: https://doi.org/10.1084/jem.20201665
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