Research ArticleGVHD

Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease

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Science Translational Medicine  18 Nov 2020:
Vol. 12, Issue 570, eabb7028
DOI: 10.1126/scitranslmed.abb7028

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Skin-deep persistence

Tissue-resident memory T cells (Trm) in the skin play a critical role in responding to environmental assaults and maintaining homeostasis. Strobl et al. characterize Trm derived from CD69+ αβ memory T cell clones in the skin of allogeneic hematopoietic stem cell transplant patients, which persisted in the skin for years after transplantation. Single-cell RNA sequencing analysis revealed that Trm had higher levels of tissue retention genes and stem cell markers. The RUNX3 transcription factor and cell surface molecule galectin-3 were defined as markers of human skin Trm. These findings delineate features of human Trm that differ from their murine counterparts and reveal a role for the skin environment in their long-term persistence.

Abstract

The skin contains a population of tissue-resident memory T cells (Trm) that is thought to contribute to local tissue homeostasis and protection against environmental injuries. Although information about the regulation, survival program, and pathophysiological roles of Trm has been obtained from murine studies, little is known about the biology of human cutaneous Trm. Here, we showed that host-derived CD69+ αβ memory T cell clones in the epidermis and dermis remain stable and functionally competent for at least 10 years in patients with allogeneic hematopoietic stem cell transplantation. Single-cell RNA sequencing revealed low expression of genes encoding tissue egress molecules by long-term persisting Trm in the skin, whereas tissue retention molecules and stem cell markers were displayed by Trm. The transcription factor RUNX3 and the surface molecule galectin-3 were preferentially expressed by host T cells at the RNA and protein levels, suggesting two new markers for human skin Trm. Furthermore, skin lesions from patients developing graft-versus-host disease (GVHD) showed a large number of cytokine-producing host-derived Trm, suggesting a contribution of these cells to the pathogenesis of GVHD. Together, our studies highlighted the relationship between the local human skin environment and long-term persisting Trm, which differs from murine skin. Our results also indicated that local tissue inflammation occurs through host-derived Trm after allogeneic hematopoietic stem cell transplantation.

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