Human resident memory T cells exit the skin and mediate systemic Th2-driven inflammation

J Exp Med. 2021 Nov 1;218(11):e20210417. doi: 10.1084/jem.20210417. Epub 2021 Oct 13.


Emigration of tissue-resident memory T cells (TRMs) was recently introduced in mouse models and may drive systemic inflammation. Skin TRMs of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) can coexist beside donor T cells, offering a unique human model system to study T cell migration. By genotyping, mathematical modeling, single-cell transcriptomics, and functional analysis of patient blood and skin T cells, we detected a small consistent population of circulating skin-derived T cells with a TRM phenotype (cTRMs) in the blood and unveil their skin origin and striking resemblance to skin TRMs. Blood from patients with active graft-versus-host disease (GVHD) contains elevated numbers of host cTRMs producing pro-inflammatory Th2/Th17 cytokines and mediating keratinocyte damage. Expression of gut-homing receptors and the occurrence of cTRMs in gastrointestinal GVHD lesions emphasize their potential to reseed and propagate inflammation in distant organs. Collectively, we describe a distinct circulating T cell population mirroring skin inflammation, which could serve as a biomarker or therapeutic target in GVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / immunology
  • Graft vs Host Disease / immunology
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunologic Memory / immunology*
  • Inflammation / immunology*
  • Keratinocytes / immunology
  • Mice
  • Skin / immunology*
  • Th17 Cells / immunology
  • Th2 Cells / immunology*
  • Transplantation, Homologous / methods


  • Cytokines