Similar Datasets
Project description: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.
2021-06-24 | GSE178768 | GEO
Project description: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.
2021-06-24 | GSE178767 | GEO
Project description: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.
2021-06-24 | GSE178766 | GEO
Project description:Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity
| PRJNA740308 | ENA
Project description:Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity (Liver)
| PRJNA740313 | ENA
Project description:Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity (Skin)
| PRJNA740314 | ENA
Project description:Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity (Salivary Gland)
| PRJNA740312 | ENA
Project description:Tissue-resident memory CD8 T cells (TRM) provide protection from infection at barrier sites. In the small intestine, TRM cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential. However, the origins of this diversity remain unknown. We proposed that distinct tissue niches drive TRM phenotypic heterogeneity. To test this, we leveraged spatial transcriptomics of human samples, a murine model of acute systemic viral infection, and a newly established strategy for pooled optically-encoded gene perturbations to profile the location, interaction, and transcriptome of pathogen-specific TRM differentiation at single-transcript resolution. We developed computational approaches to capture cellular locations along three anatomical axes of the small intestine and to visualize the spatiotemporal distribution of cell types and gene expression. Our study reveals that the intestinal architecture’s regionalized signaling supports two distinct TRM cell states: differentiated TRM and progenitor-like TRM cells, located in the upper versus lower villus, respectively. This diversity is mediated by distinct ligand-receptor activities, cytokine gradients, and specialized cellular contacts. Blocking TGFb or Cxcl9/10-sensing by antigen-specific CD8 T cells revealed a model consistent with anatomically delineated early fate specification. Ultimately, our framework for the study of tissue immune networks has revealed that T cell location and functional state are fundamentally intertwined.
2024-11-11 | GSE280895 | GEO
Project description:Tissue resident memory CD8 T cells (TRM) serve as potent local sentinels and contribute significantly to protective immunity against intracellular mucosal pathogens. While the molecular and transcriptional underpinnings of TRM differentiation are emerging, how TRM establishment is regulated by other leukocytes in vivo is largely unclear. Here, we observed that expression of PPAR-γ in the myeloid compartment was a negative regulator of CD8 TRM establishment following influenza virus infection. Interestingly, myeloid deficiency of PPAR-γ resulted in selective impairment of the tissue-resident alveolar macrophage (AM) compartment during primary influenza infection, suggesting that AM are likely negative regulators of CD8 TRM differentiation. Indeed, influenza-specific CD8 TRM cell numbers were increased following early, but not late ablation of AM using the CD169-DTR model. Importantly, these findings were specific to the parenchyma of infected tissue as circulating memory T cell frequencies in lung and TCM and TEM in spleen were largely unaltered following macrophage ablation. Further, the magnitude of the effector response could not explain these observations. These data indicate local regulation of pulmonary TRM differentiation is alveolar macrophage dependent. These, findings could aid in vaccine design aimed at increasing TRM density to enhance protective immunity, or deflating their numbers in conditions where they cause overt or veiled chronic pathologies.
| S-EPMC6797929 | biostudies-literature
Project description:Recent studies have shown that tissue resident memory T cells (T(RM)) are critical to antiviral host defense in peripheral tissues. This new appreciation of T(RM) that reside in epithelial tissues and mediate host defense has been studied most extensively in skin: adult human skin contains large numbers of functional T(RM) that express skin specific markers. Indeed, more than twice as many T cells reside in skin as in peripheral blood. This T cell population has a diverse T cell receptor repertoire, and can produce a broad array of cytokines. More recently, we have begun to examine other epithelial tissues for the presence of resident T cells. In the present study, we asked whether analogous populations of resident T cells could be found in human lung. We were able to demonstrate abundant resident T cells in human lung-more than 10 billion T cells were present. Lung T cells were largely of the effector memory T cell (T(EM)) phenotype, though small numbers of central memory T cells (T(CM)) and T regulatory cells (T(reg)) could be identified. Lung T cells had a diverse T cell receptor repertoire and subsets produced IL-17, IL-4, IFN?, as well as TNF?. A significant number of lung T(RM) CD4+Th cells produced more than one cytokine, identifying them as "multifunctional" Th1 type cells. Finally, lung T(RM), but not T(RM) resident to skin or T cells from blood, proliferated in response to influenza virus. This work suggests that normal human lung contains large numbers of T(RM) cells, and these cells are poised to respond to recall antigens previously encountered through lung mucosa. This population of T cells may contribute to the pathogenesis of asthma and other T cell mediated lung diseases.
| S-EPMC3027667 | biostudies-other