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Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity (Skin)

ABSTRACT: Tissue-resident memory T cells (TRM) are non-recirculating cells that exist throughout the body. While TRM in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here, we chart TRM heterogeneity between organs and find that the different environments in which these cells differentiate dictate TRM function, durability and malleability. We find that unequal responsiveness to TGF-β is a major driver of this diversity. Strikingly, dampened TGF-b signaling engendered CD103- TRM with increased proliferative potential, enhanced function, and reduced longevity compared to their TGF-β-responsive CD103+ TRM counterparts. Further, while CD103- TRM readily modified their phenotype upon relocation, CD103+ TRM were comparatively resistant to trans-differentiation. Thus, despite common requirements for TRM development, adaptation of these cells to their tissue of residence confers discrete functional properties such that TRM exist along a spectrum of differentiation potential that is governed by their local microenvironment.

ORGANISM(S): Mus musculus

PROVIDER: GSE178768 | GEO | 2021/06/24

REPOSITORIES: GEO

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Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity (Liver)

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Project description:We report the transcriptome analysis of epidermal CD8 tissue resident memory T (TRM) cells from healthy human skin. Specifically, epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells from healthy human skin were sorted by FACS. Differential gene expression analysis revealed functional dichotomy of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells.

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Retinoic acid signaling during priming licenses intestinal CD103+ CD8 TRM cell differentiation

Project description:CD8 tissue-resident memory T (TRM) cells provide front-line protection at barrier tissues; however, mechanisms regulating TRM cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.

2023-02-13 | GSE223983 | GEO

Molecular signature of brain resident memory CD8+ T cells

Project description:Tissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment. 13 samples were analyzed: 5 replicates of memory OT-I CD8+.CD103- T cells isolated from the spleen of mice on day 20 p.i. with VSV-OVA. 5 replicates of memory OT-I CD8+CD103+ T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA; and 3 replicates of memory OT-I.CD8+ CD103- T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA

2012-08-29 | E-GEOD-39152 | biostudies-arrayexpress

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