Stem-like memory-T maintenance and differentiation into tissue-resident T cells sustain chronic graft-versus-host disease in mice - PubMed
5 hours ago
- #inflammation
- #memory T cells
- #chronic GVHD
- The study identifies four donor-type CD4+ memory T cell (Tm) subsets in chronic graft-versus-host disease (GVHD) in mice: stem-like memory T cells (Tsm), resident memory progenitor T cells (Trmp), terminally differentiated tissue-resident T cells (Trm), and intermediate T cells (Tint).
- Trm cells exhibit highly biased clonotypes and high proinflammatory cytokine expression, indicating their role in sustaining chronic inflammation.
- Tsm cells require TCR-MHCII interactions for maintenance and expansion, showing greater self-renewal capacity, generation of Trm, and pathogenicity compared to Trmp cells.
- Transcription factors TCF1/BCL6 and BHLHE40 differentially regulate Tsm stemness and differentiation into Trm, respectively. Targeting these factors reduces Trm numbers and inflammation.
- The findings suggest that targeting the Tsm subset could be an effective approach to treat T cell-mediated chronic inflammation.