The link between tissue-resident memory T cells and graft-versus-host disease

In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), this review outlines and analyzes recent developments in the understanding of the properties of tissue-resident memory T cells (TRMs). The paper first discusses commonly recognized TRM characteristics and key TRM phenotypic markers and then covers the master transcription factors controlling TRM generation and maintenance. The TRM distribution in graft-versus-host disease (GVHD)-targeted organs and correlations between allo-HSCT outcomes and various GVHD subtypes were also reviewed, mainly focusing on skin and gut GVHD. This review discusses the organ- and tissue-specific characteristics of donor- and recipient-derived TRMs after allo-HSCT. It also highlights investigations using murine GVHD models, nonhuman primates, and cutting-edge technologies to track clonotypes, establish transcriptome profiles, and identify donor- and recipient-derived TRMs. Furthermore, this review discusses significant results for TRM functions in GVHD patients. Moreover, potential advantages of performing GVHD-focused TRM research with "dirty mice" rather than laboratory mice were proposed. Understanding TRMs in allo-HSCT is a rapidly growing field requiring future studies to address unresolved questions regarding TRM heterogeneity, plasticity, longevity, alloreactivity, and roles in GVHD and tolerance after allo-HSCT.