Epidermal Resident Memory T Cell Fitness Requires Antigen Encounter in the Skin
Abstract CD8+ tissue resident memory T cells (TRM) develop from effectors that seed peripheral tissues where they persist providing defense against subsequent challenges. TRM persistence requires autocrine TGFβ transactivated by integrins expressed on keratinocytes. TRM precursors that encounter antigen in the epidermis during development outcompete bystander TRM for TGFβ resulting in enhanced persistence. ScRNA-seq analysis of epidermal TRM revealed that local antigen experience in the skin resulted in an enhanced differentiation signature in comparison with bystanders. Upon recall, TRM displayed greater proliferation dictated by affinity of antigen experienced during epidermal development. Finally, local antigen experienced TRM differentially expressed TGFβRIII, which increases avidity of the TGFβRI/II receptor complex for TGFβ. Selective ablation of Tgfbr3 reduced local antigen experienced TRM capacity to persist, rendering them phenotypically like bystander TRM. Thus, antigen driven TCR signaling in the epidermis during TRM differentiation results in a lower TGFβ requirement for persistence and increased proliferative capacity that together enhance epidermal TRM fitness.
Authors
- Susan C. Baker (ORCID: https://orcid.org/0000-0001-6485-8143)
- Kazuo Kurihara (ORCID: https://orcid.org/0000-0003-4964-1549)
- David Zemmour (ORCID: https://orcid.org/0000-0002-0990-217X)
- Harinder Singh (ORCID: https://orcid.org/0000-0002-6330-8526)
- Y. Zhang (ORCID: https://orcid.org/0009-0001-2327-0623)
- Andrew W. Liu (ORCID: https://orcid.org/0000-0003-2355-5888)
- Toshiro Hirai (ORCID: https://orcid.org/0000-0002-9212-1664)
- Laura K. Mackay (ORCID: https://orcid.org/0000-0002-8496-6632)
- Haiyue Li (ORCID: https://orcid.org/0000-0001-9901-3714)
- Jacob E. Gillis (ORCID: https://orcid.org/0000-0001-6248-693X)
- Niroshana Anandasabapathy (ORCID: https://orcid.org/0000-0002-0473-8358)
- Daniel H. Kaplan (ORCID: https://orcid.org/0000-0003-0598-0047)
- Torben Ramcke (ORCID: https://orcid.org/0000-0001-5616-845X)
- David Masopust (ORCID: https://orcid.org/0000-0002-9440-3884)
- Ian Magill (ORCID: https://orcid.org/0009-0009-1280-3365)
- E. H. Weiss (ORCID: https://orcid.org/0000-0003-2352-0036)
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- The University of Melbourne (AU)
- University of Pittsburgh (US)
- Cornell University (US)
- Peter Doherty Institute (AU)
- University of Minnesota Medical Center (US)
- The University of Osaka (JP)
Publication Details
- Journal
- eLife
- Published
- 2025-09-29
- DOI
- https://doi.org/10.7554/elife.107096.2
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00