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

Area of Science:

• Immunology
• Cell Biology
• Transplantation Science

Background:

• Tissue-resident memory T cells (TRMs) emigration may drive systemic inflammation.
• Allogeneic hematopoietic stem cell transplantation (HSCT) patients offer a model to study T cell migration.
• Skin TRMs can coexist with donor T cells post-HSCT.

Purpose of the Study:

• To investigate the origin and phenotype of circulating T cells in HSCT patients.
• To determine the role of these cells in graft-versus-host disease (GVHD).
• To explore potential biomarkers and therapeutic targets for GVHD.

Main Methods:

• Genotyping and mathematical modeling.
• Single-cell transcriptomics and functional analysis of patient blood and skin T cells.
• Analysis of T cell populations in patients with active GVHD.

Main Results:

• A distinct population of circulating skin-derived T cells (cTRMs) with TRM phenotype was identified.
• Elevated cTRM numbers were found in patients with active GVHD, producing pro-inflammatory cytokines.
• cTRMs express gut-homing receptors and are present in gastrointestinal GVHD lesions.

Conclusions:

• cTRMs represent a circulating T cell population mirroring skin inflammation.
• These cells may reseed and propagate inflammation in distant organs, particularly in GVHD.
• cTRMs could serve as a biomarker or therapeutic target for GVHD.