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<p>Tissue-resident memory T (T<sub>RM</sub>) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. T<sub>RM</sub> 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<sup>+</sup> T<sub>RM</sub> cells in the skin. PD-1 is expressed broadly across mouse and human skin T<sub>RM</sub> cells, in the absence of persistent infection, and is retained on skin T<sub>RM</sub> cells in aged mice. PD-1 supports early T<sub>RM</sub> 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<sub>RM</sub> cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.</p>

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PD-1 is requisite for skin TRM cell formation and specification by TGFβ

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月29日

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  • 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

摘要

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.