PD-1 is requisite for skin T(RM) cell formation and specification by TGFβ

Devi, KSP; Wang, E; Jaiswal, A; Konieczny, P; Kim, TG; Nirschl, CJ; Verma, A; Liu, Y; Milczanowski, J; Christo, SN; Gandolfo, LC; Haitz, K; Vardam, TD; Wu, P; King, SL; Tse, SW; Pradhan, K; Jiang, X; Tian, T; Fuhlbrigge, RC; Schmults, CD; Clark, RA; Kupper, TS; Freeman, GJ; Mackay, LK; Naik, S; Newell, EW; Elemento, O; Suarez-Farinas, M; Anandasabapathy, N

Author(s): Devi, KSP; Wang, E; Jaiswal, A; Konieczny, P; Kim, TG; Nirschl, CJ; Verma, A; Liu, Y; Milczanowski, J; Christo, SN; Gandolfo, LC; Haitz, K; Vardam, TD; Wu, P; King, SL; Tse, SW; Pradhan, K; Jiang, X; Tian, T; Fuhlbrigge, RC; Schmults, CD; Clark, RA; Kupper, TS; Freeman, GJ; Mackay, LK; Naik, S; Newell, EW; Elemento, O; Suarez-Farinas, M; Anandasabapathy, N;
Details: Publication Year 2025-08,Volume 26,Issue #8,Page 1339-1351
Journal Title: Nature Immunology
Abstract: Tissue-resident memory T (T(RM)) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. T(RM) cells are implicated in autoimmunity, successful response to immune checkpoint blockade in the tumor microenvironment and toxicities that occur after immune checkpoint blockade in peripheral tissues. Here, we identified that signaling through the immune checkpoint programmed death receptor 1 (PD-1) strongly impacts the early specification of CD8(+) T(RM) cells in the skin. PD-1 is expressed broadly across mouse and human skin T(RM) cells, in the absence of persistent infection, and is retained on skin T(RM) cells in aged mice. PD-1 supports early T(RM) cell colonization, skin-specific programming and silencing of other differentiation programs and promotes TGFβ responsivity and skin engraftment. Thus, PD-1 signaling mediates skin T(RM) cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.
Publisher: Springer Nature
Keywords: *Programmed Cell Death 1 Receptor/metabolism/immunology/genetics; Animals; *Transforming Growth Factor beta/metabolism/immunology; *Skin/immunology/cytology; Mice; Humans; *Immunologic Memory; *CD8-Positive T-Lymphocytes/immunology; Mice, Inbred C57BL; Signal Transduction/immunology; *Memory T Cells/immunology; Mice, Knockout; Cell Differentiation/immunology; Female
Research Division(s): Bioinformatics and Computational Biology
PubMed ID: 40730902
Publisher's Version: https://doi.org/10.1038/s41590-025-02228-1
Open Access at Publisher's Site: https://doi.org/10.1038/s41590-025-02228-1
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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