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Intestinal CD103- Trm cells are first responders to secondary infection

ABSTRACT: To address both the plasticity of intestinal Trm subsets and their unique contributions to tissue and systemic immunity, we have generated mice to fate map CD103+ Trm cells after primary infection and follow their location and functionality during secondary infection. We found that the intestinal CD103– Trm subset are the primary responders to secondary infection and observed limited expansion of the CD103+ Trm subset. To understand the unique features of CD103– Trm cells that allow this population to respond more quickly to secondary infection and to understand the gene expression changes that accompany Trm reactivation, we performed RNA-sequencing on CD103+Tomato+ and CD103–Tomato– LP Trm cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE185541 | GEO | 2022/09/12

REPOSITORIES: GEO

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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

An unconventional integrin b3 and CD103 heterodimer improves the anti-tumor immunity of tissue-resident T cells

Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.

2024-02-14 | PXD031794 | Pride

RNA-seq transcriptome analysis of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- T cells from healthy human skin

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.

2017-02-14 | GSE83637 | GEO

Secondary infections regenerate the intestinal CD103+ tissue-resident memory T-cell pool

Project description:Using a novel fate-mapping approach, we identified that resident intestinal CD103 expressing T-cells lack secondary expansion potential and are replaced by de novo formed cells during re-infection.

2022-11-22 | GSE208097 | GEO

Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects

Project description:Tissue-resident memory T cells (TRM) persist locally in non-lymphoid tissues where they provide front-line defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69 which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to re-enter the circulation and potentially migrate to distant tissue sites have been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can downregulate CD69 and exit the tissue. Additionally, we identified a skin-tropic CD4+CD69-CD103+ population in human lymph and blood that is transcriptionally, functionally and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can re-enter circulation, and migrate to secondary human skin sites where they re-assume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.

2019-05-25 | GSE131770 | GEO

Depleting CD103+ resident memory T cells in vivo reveals immunostimulatory functions in oral mucosa

Project description:The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues and mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report that the oral mucosa harbors CD8+ CD103+ resident memory T cells (TRM), which locally survey tissues without recirculating. Oral antigen reencounter during the effector phase of immune responses potentiated TRM establishment within tongue, gums, palate, and cheek. Upon reactivation, oral TRM triggered changes in somatosensory and innate immune gene expression. We developed in vivo methods for depleting CD103+ TRM while sparing CD103neg TRM and recirculating cells. This revealed that CD103+ TRM were responsible for inducing local gene expression changes. Oral TRM putatively protected against local viral infection. This study provides methods for generating, assessing, and in vivo depleting oral TRM, documents their distribution throughout the oral mucosa, and provides evidence that TRM confer protection and trigger responses in oral physiology and innate immunity.

2023-04-18 | GSE229634 | GEO

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets I

Project description:Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating these two CD8+ populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft and lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103- TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.

2020-12-05 | GSE162685 | GEO

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets II

2020-12-05 | GSE162686 | GEO

SKI-dependent TGFb signaling dictates CD103 expression in CD8+ T cells (ChIP-seq)

Project description:Initially identified as a functional marker for resident-memory (Trm) CD8+ T cells, CD103 (encoded by ITGAE gene) has broad roles in immunity and diseases. Elucidating the function and regulation of CD103 is thus of importance. This study revealed that the CD103 expression by CD8 T cells under steady state contributes to the clearance of acute viral infection. More importantly, it discovered TGF-SKI-Smad4 a critical signaling axis in restricting CD103 expression in CD8+ T cells for their function. Mechanistically, by ChIP-Seq and ChIP analysis, SKI associated with Smad4 was found to directly and epigenetically suppress CD103 transcription. This study therefore reveals a novel TGF-SKI-Smad4 pathway to specifically enable CD103 expression in CD8+ T cells for protective immunity.

2020-07-28 | GSE135533 | GEO

Development pathway for skin resident memory CD103+CD8+ T cells

Project description:Tissue resident memory T cells (TRM) provide superior protection against infection localised to extra-lymphoid compartments in the body. Here we show that CD103+CD8+ TRM cells develop in skin from killer cell lectin-like receptor (KLR)G1-negative precursors that selectively infiltrate the epithelial layer. In the skin, a combination of chemokine-guided epithelial entry, local interleukin (IL)-15 and transforming growth factor (TGF)-Î² signalling is required for formation and survival of these long-lived memory cells. Importantly, TRM differentiation results in the gradual acquisition of a unique transcriptional profile that differs from that expressed by memory cells in the circulation and other types of skin-resident intra-epithelial T cells, such as the dendritic epidermal T cells (DETC). We provide a comprehensive molecular and developmental framework for the local differentiation of a distinct type of peripheral memory T cell that contributes to an important first-line of immune defence in barrier tissues such as skin and mucosa. 24 samples were analyzed: 3 replicates of memory gB-T CD8+. CD103+ T cells isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of memory P14 CD8+ T cells isolated from gut of mice on day 60 p.i. with LCMV Armstrong. 3 replicates of memory gB-T CD8+ T cells from the lung of mice on day 30 p.i. with influenza WSN. 3 replicates of memory CD62L high CD8+ T cells from the spleen of mice on day 30 p.i. with HSV KOS. 3 replicates of memory CD62L low CD8+ T cells from the spleen of mice of day 30 p.i. with HSV KOS. 3 replicates of Î³Î´-DETC isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of Î±Î²-DETC from naive TCRÎ´-/- mice; and 3 replicates of naive gB-T CD8+ T cells from the spleen of naive gB-T transgenic mice.

2013-10-01 | E-GEOD-47045 | biostudies-arrayexpress

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