Disruption of skin homeostasis reveals divergent reconstitution dynamics of human skin tissue-resident memory T cell subsets
Tissue-resident memory T cells (TRM) maintain homeostasis while also driving inflammatory conditions but underlying regulatory dynamics in humans are poorly understood. Here, we investigate human skin TRM biology in a unique clinical setting: patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), with or without graft-versus-host disease (GVHD). Using single-cell RNA and TCR sequencing, as well as SNP-based genotype demultiplexing, we employ a bioinformatic pipeline to comprehensively explore host and donor TRM. While skin harbors various TRM subsets in steady-state, type 17-polarized TRM (TRM17) are sharply reduced after transplantation, and type 1-polarized T cells dominate in GVHD lesions. TRM17 only recover late after transplantation, once homeostasis is restored. These insights highlight the adaptive plasticity of human skin TRM and propose their balance as prerequisite for tissue homeostasis.