Year: 2025
Type: article
Abstract: Tissue-resident memory T (TRM) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. TRM 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+ TRM cells in the skin. PD-1 is expressed broadly across mouse and human skin TRM cells, in the absence of persistent infection, and is retained on skin TRM cells in aged mice. PD-1 supports early TRM cell colonization, skin-specific programming and silencing of other differentiation programs and promotes TGFβ responsivity and skin engraftment. Thus, PD-1 signaling mediates skin TRM cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory. Anandasabapathy and colleagues show that the inhibitory receptor PD-1 impacts the specification of tissue-resident memory T cells in the skin.
Source: Nature Immunology
Authors: K. Sanjana P. Devi, Eric Wang, Abhinav Jaiswal, Piotr Konieczny, Tae-Gyun Kim, Christopher J. Nirschl, Akanksha Verma, Yong Liu, Julia Milczanowski, Susan N. Christo, Luke C. Gandolfo, Karyn Haitz, Trupti D. Vardam, Pinru Wu, Sandra L. King, Sze-Wah Tse, Komal Pradhan, Xiaodong Jiang, Tian Tian, Robert C. Fuhlbrigge, Chrysalyne D. Schmults, Rachael A. Clark, Thomas S. Kupper, Gordon J. Freeman, Laura K. Mackay, Shruti Naik, Evan W. Newell, Olivier Elemento, Mayte Suarez-Farinas, Niroshana Anandasabapathy
Institutions: Weill Cornell Medicine, Icahn School of Medicine at Mount Sinai, Yonsei University, Brigham and Women's Hospital, Harvard University, The University of Melbourne, Peter Doherty Institute, Walter and Eliza Hall Institute of Medical Research, Mayo Clinic, Mayo Clinic in Arizona, Dana-Farber Brigham Cancer Center, Dana-Farber Cancer Institute, Fred Hutch Cancer Center
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: New York Stem Cell Foundation, Melanoma Research Alliance, Brigham and Women's Hospital, National Institutes of Health, Weill Cornell Medical College, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: CTCL immunobiology: lessons from alemtuzumab, G3504414196, G3914049566, Transforming the diagnosis and care of patients with CTCL using TCR sequencing, Decoding microbe-epithelial stem cell interactions in health and disease, Skin Homing T Cells -- Molecular Characterization of CLA, Harnessing the effects of Ror gamma t cells on epidermal stem cells and commensal microbes to promote efficient wound repair, G6617120125, Vaccination to generate protective tissue resident T cells, Decoding the repair and immunomodulatory functions of lymphatic vessels in wound healing, T Cell Costimulatory Pathways: Functions and Interactions, G8192181922, New mechanisms governing skin tissue residency memory T cells, Mechanisms of immune-epithelial crosstalk in tissue repair, Dermatology Training Grant, Interrogating unique DC adaptations to tissue to promote barrier immunity and tolerance
OpenAlex ID: W4412709704