Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TIGIT Deficiency Protects Mice From DSS-Induced Colitis by Regulating IL-17A–Producing CD4+ Tissue-Resident Memory T Cells

ABSTRACT: Tissue-resident memory T cells (TRM cells) have been shown to play an instrumental role in providing local immune responses for pathogen clearance in barrier tissues. However, their contribution to inflammatory bowel diseases (IBDs) and the underlying regulation are less clear. Here, we identified a critical role of T-cell immunoreceptor with immunoglobulin and ITIM (TIGIT) in regulating CD4+ TRM cells in an experimental model of intestinal inflammation. We found that CD4+ TRM cells were increased and correlated with disease activities in mice with dextran sulfate sodium (DSS)-induced colitis. Phenotypically, these CD4+ TRM cells could be classified into CD69+CD103− and CD69+CD103+ subsets. Functionally, these CD4+ TRM cells were heterogeneous. CD69+CD103− CD4+ TRM cells were pro-inflammatory and produced interferon-γ (IFNγ) and interleukin-17A (IL-17A), which accounted for 68.7% and 62.9% of total IFNγ+ and IL-17A+ CD4+ T cells, respectively, whereas CD69+CD103+ CD4+ TRM cells accounted for 73.7% Foxp3+ regulatory T cells. TIGIT expression was increased in CD4+ T cells in the gut of mice with DSS-induced colitis. TIGIT deficiency impaired IL-17A expression in CD69+CD103− CD4+ TRM cells specifically, resulting in ameliorated gut inflammation and tissue injury. Together, this study provides new insights into the regulation of gut inflammation that TIGIT deficiency protects mice from DSS-induced colitis, which might have a potential therapeutic value in the treatment of IBDs.

SUBMITTER: Chen B

PROVIDER: S-EPMC9283574 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation.

Project description:The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4+CD45RBhigh T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4+ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4+ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4+ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

| S-EPMC6695484 | biostudies-literature

The IL-27 receptor regulates TIGIT on memory CD4+ T cells during sepsis.

Project description:Sepsis is a leading cause of morbidity and mortality associated with significant impairment in memory T cells. These changes include the upregulation of co-inhibitory markers, a decrease in functionality, and an increase in apoptosis. Due to recent studies describing IL-27 regulation of TIGIT and PD-1, we assessed whether IL-27 impacts these co-inhibitory molecules in sepsis. Based on these data, we hypothesized that IL-27 was responsible for T cell dysfunction during sepsis. Using the cecal ligation and puncture (CLP) sepsis model, we found that IL-27Rα was associated with the upregulation of TIGIT on memory CD4+ T cells following CLP. However, IL-27 was not associated with sepsis mortality.

| S-EPMC7881227 | biostudies-literature

Transcriptomic analysis reveals a controlling mechanism for NLRP3 and IL-17A in dextran sulfate sodium (DSS)-induced colitis.

Project description:The incidence of inflammatory bowel disease (IBD) has markedly increased. Our research findings during the past showed that medicinal plant extracts and the derived phytochemical components from Wedelia chinensis (WC) can have strong anti-colitis activities. Here, we further identified the key component phytochemicals from active fractions of different WC preparations (WCHA) that are responsible for the protective effect of WCHA in colitis mice. Of the 3 major compounds (wedelolactone, luteolin and apigenin) in this fraction, luteolin had the highest anti-inflammatory effect in vivo. Using a next-generation sequencing (NGS) (e.g., RNA-seq) system to analyze the transcriptome of colorectal cells/tissues in mice with dextran sulfate sodium (DSS)-induced colitis with/without phytochemicals treatment, luteolin was found to strongly suppress the DSS-activated IL-17 pathway in colon tissue. In addition, co-treatment with wedelolactone and luteolin had a synergistic effect on the expression level of some IL-17 pathway-related genes. Interestingly, our NGS analyses also indicated that luteolin and wedelolactone can specifically suppress the expression of NLRP3 and NLRP1. Using a 3-dimensional cell co-culture system, we further demonstrated that luteolin could efficiently suppress NLRP3 expression via disruption of IL-17A signaling in inflamed colon tissue, which also indicates the pharmacological potential of luteolin and wedelolactone in treating IBD.

| S-EPMC6175949 | biostudies-literature

NK1.1- CD4+ NKG2D+ T cells suppress DSS-induced colitis in mice through production of TGF-β.

Project description:CD4+ NKG2D+ T cells are associated with tumour, infection and autoimmune diseases. Some CD4+ NKG2D+ T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4+ NKG2D+ T cells were further classified into NK1.1- CD4+ NKG2D+ and NK1.1+ CD4+ NKG2D+ subpopulations. The frequency of NK1.1- CD4+ NKG2D+ cells decreased in inflamed colons, whereas more NK1.1+ CD4+ NKG2D+ cells infiltrated into colons of mice with DSS-induced colitis. NK1.1- CD4+ NKG2D+ cells expressed TGF-β and FasL without secreting IFN-γ, IL-21 and IL-17 and displayed no cytotoxicity. The adoptive transfer of NK1.1- CD4+ NKG2D+ cells suppressed DSS-induced colitis largely dependent on TGF-β. NK1.1- CD4+ NKG2D+ cells did not expressed Foxp3, CD223 (LAG-3) and GITR. The subpopulation was distinct from NK1.1+ CD4+ NKG2D+ cells in terms of surface markers and RNA transcription. NK1.1- CD4+ NKG2D+ cells also differed from Th2 or Th17 cells because the former did not express GATA-3 and ROR-γt. Thus, NK1.1- CD4+ NKG2D+ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.

| S-EPMC5487917 | biostudies-literature

Obesity-induced dysregulation of skin-resident PPARγ+ Treg cells promotes IL-17A-mediated psoriatic inflammation.

Project description:Obesity is a major risk factor for psoriasis, but how obesity disrupts the regulatory mechanisms that keep skin inflammation in check is unclear. Here, we found that skin was enriched with a unique population of CD4+Foxp3+ regulatory T (Treg) cells expressing the nuclear receptor peroxisome proliferation-activated receptor gamma (PPARγ). PPARγ drove a distinctive transcriptional program and functional suppression of IL-17A+ γδ T cell-mediated psoriatic inflammation. Diet-induced obesity, however, resulted in a reduction of PPARγ+ skin Treg cells and a corresponding loss of control over IL-17A+ γδ T cell-mediated inflammation. Mechanistically, PPARγ+ skin Treg cells preferentially took up elevated levels of long-chain free fatty acids in obese mice, which led to cellular lipotoxicity, oxidative stress, and mitochondrial dysfunction. Harnessing the anti-inflammatory properties of these PPARγ+ skin Treg cells could have therapeutic potential for obesity-associated inflammatory skin diseases.

| S-EPMC10527179 | biostudies-literature

IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue.

Project description:T helper type (Th17) cytokines such as interleukin (IL)-17A and IL-22 are important in maintaining mucosal barrier function and may be important in the pathogenesis of inflammatory bowel diseases (IBDs). Here, we analyzed cells from the colon of IBD patients and show that Crohn's disease (CD) patients had significantly elevated numbers of IL-17+, CD4+ cells compared with healthy controls and ulcerative colitis (UC) patients, but these numbers did not vary based on the inflammatory status of the mucosa. By contrast, UC patients had significantly reduced numbers of IL-22+ cells in actively inflamed tissues compared with both normal tissue and healthy controls. There was a selective increase in mono-IL-17-producing cells from the mucosa of UC patients with active inflammation together with increased expression of transforming growth factor (TGF)-? and c-Maf. Increasing concentrations of TGF-? in lamina propria mononuclear cell cultures significantly depleted Th22 cells, whereas anti-TGF-? antibodies increased IL-22 production. When mucosal microbiota was examined, depletion of Th22 cells in actively inflamed tissue was associated with reduced populations of Clostridiales and increased populations of Proteobacteria. These results suggest that increased TGF-? during active inflammation in UC may lead to the loss of Th22 cells in the human intestinal mucosa.

| S-EPMC3870042 | biostudies-literature

Upregulation of Intestinal Barrier Function in Mice with DSS-Induced Colitis by a Defined Bacterial Consortium Is Associated with Expansion of IL-17A Producing Gamma Delta T Cells.

Project description:Bacterial consortium transplantation (BCT) is a promising alternative to fecal microbiota transplantation in treating inflammatory bowel disease (IBD). Here, we showed that a defined bacterial consortium derived from healthy mice was able to enhance the intestinal barrier function of mice with dextran sulfate sodium (DSS)-induced colitis. Interestingly, we found that the bacterial consortium significantly promoted the expansion of IL-17A-producing ??T (??T17) cells in colonic lamina propria, which was closely associated with changing of intestinal microbial composition. The increased IL-17A secretion upon treatment with microbial products derived from the bacterial consortium was accompanied with upregulation of TLR2 expression by ??T cells, and it might be responsible for the upregulation of mucosal barrier function through IL-17R-ACT1-mediated recovery of the disrupted occludin subcellular location. Changing of some specific microbial groups such as Bifidobacterium and Bacillus spp. was closely correlated with the promotion of TLR2+ ??T cells. Our results support that BCT can restore the alliance between commensal microbiota and intestinal ??T cells, which contributes to the improvement of intestinal barrier function. This study provides new insight into the development of bacteria transplantation therapy for the treatment of IBD.

| S-EPMC5506203 | biostudies-literature

IL-17A and IL-17F producing cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-20 | GSE189232 | GEO

IL-17A-producing resident memory γδ T cells orchestrate the innate immune response to secondary oral Listeria monocytogenes infection.

Project description:Memory γδ T cells are important for the clearance of Listeria monocytogenes infection in the intestinal mucosa. However, the mechanisms by which memory γδ T cells provide protection against secondary oral infection are poorly understood. Here we used a recombinant strain of L. monocytogenes that efficiently invades the intestinal epithelium to show that Vγ4(+) memory γδ T cells represent a resident memory (Trm) population in the mesenteric lymph nodes (MLNs). The γδ Trm exhibited a remarkably static pattern of migration that radically changed following secondary oral L. monocytogenes infection. The γδ Trms produced IL-17A early after rechallenge and formed organized clusters with myeloid cells surrounding L. monocytogenes replication foci only after a secondary oral infection. Antibody blocking studies showed that in addition to IL-17A, the chemokine receptor C-X-C chemokine receptor 3 (CXCR3) is also important to enable the local redistribution of γδ Trm cells and myeloid cells specifically near the sites of L. monocytogenes replication within the MLN to restrict bacterial growth and spread. Our findings support a role for γδ Trms in orchestrating protective immune responses against intestinal pathogens.

| S-EPMC4968747 | biostudies-literature

Interleukin (IL)-17A and IL-22-producing neutrophils in psoriatic skin.

Project description: Not available

| S-EPMC5921865 | biostudies-literature