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.
Human resident memory T cells exit the skin and mediate systemic Th2-driven inflammation
Disclosures: The authors declare no competing interests exist.
- Award Id(s): 17872
- Award Id(s): P31494
- Award Id(s): IF_2017_29
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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; Human resident memory T cells exit the skin and mediate systemic Th2-driven inflammation. J Exp Med 1 November 2021; 218 (11): e20210417. doi: https://doi.org/10.1084/jem.20210417
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