Human resident memory T cells exit the skin and mediate systemic Th2-driven inflammation
Johanna Strobl, Laura Marie Gail, Lisa Kleißl, Ram Vinay Pandey, Valerie Smejkal, Julian Huber, Viktoria Puxkandl, Luisa Unterluggauer, Ruth Dingelmaier‐Hovorka, Denise Atzmüller, Thomas Krausgruber, Christoph Bock, Philipp Wohlfarth, Werner Rabitsch, Georg Stary
Abstract
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.