Similar Datasets
Project description:T cells in mucosal tissues fulfill a complex array of duties to ensure maintenance of barrier immunity. In oral mucosa tissue, we found that increased inflammation altered CD4 T cell subsets in a spatially-dependent manner, although it had a modest effect on the frequency of tissue-resident memory T cells (TRM) and the CD4 T cell transcriptome. In contrast, localization to the tissue profoundly altered the transcriptional profile, emphasizing the importance of studying healthy tissue to understand disease-specific changes. Our data revealed the existence of a TH17 cell population that is predominantly found in the tissue-resident, but not transient, CD4 T cell compartment in mucosal tissue.
2019-12-08 | GSE116130 | GEO
Project description:T cells in mucosal tissues fulfill a complex array of duties to ensure maintenance of barrier immunity. In oral mucosa tissue, we found that increased inflammation altered CD4 T cell subsets in a spatially-dependent manner, although it had a modest effect on the frequency of tissue-resident memory T cells (TRM) and the CD4 T cell transcriptome. In contrast, localization to the tissue profoundly altered the transcriptional profile, emphasizing the importance of studying healthy tissue to understand disease-specific changes. Our data revealed the existence of a TH17 cell population that is predominantly found in the tissue-resident, but not transient, CD4 T cell compartment in mucosal tissue.
2019-12-08 | GSE116139 | GEO
Project description:A human TH17 population with a tissue-resident signature in healthy and inflamed oral mucosal tissues
| PRJNA477368 | ENA
Project description:A human TH17 population with a tissue-resident signature in healthy and inflamed oral mucosal tissues [10x]
| PRJNA477354 | ENA
Project description:A human TH17 population with a tissue-resident signature in healthy and inflamed oral mucosal tissues [Bulk RNA-seq]
| PRJNA477371 | ENA
Project description:Keeping a stable equilibrium between the host and commensal microbes to which we are constantly exposed, poses a major challenge for the immune system. The host mechanisms that regulate homeostasis of the microbiota to prevent infection and inflammatory disorders are not fully understood. Here, we provide evidence that CD4+ tissue-resident memory T (TRM) cells act as central players in this process. Using a murine model of C. albicans commensalism we show that IL-17 producing CD69+CD103+CD4+ memory T cells persist in the colonized tissue long-term and independently of circulatory supplies. Consistent with the requirement of Th17 cells for limiting fungal growth, IL-17-producing TRM cells in the mucosa were sufficient to maintain prolonged colonization, while circulatory T cells were dispensable. Although TRM cells were first proposed to protect from pathogens causing recurrent acute infections, our results support a central function of TRM cells in the maintenance of commensalism.
| S-EPMC7946631 | biostudies-literature
Project description:T helper 17 (Th17) cells are pathogenic in many inflammatory diseases, but also support the integrity of the intestinal barrier in a non-inflammatory manner. It is unclear what distinguishes inflammatory Th17 cells elicited by pathogens and tissue-resident homeostatic Th17 cells elicited by commensals. Here, we compared the characteristics of Th17 cells differentiating in response to commensal bacteria (SFB) to those differentiating in response to a pathogen (Citrobacter rodentium). Homeostatic Th17 cells exhibited little plasticity towards expression of inflammatory cytokines, were characterized by a metabolism typical of quiescent or memory T cells, and did not participate in inflammatory processes. In contrast, infection-induced Th17 cells showed extensive plasticity towards pro-inflammatory cytokines, disseminated widely into the periphery, and engaged aerobic glycolysis in addition to oxidative phosphorylation typical for inflammatory effector cells. These findings will help ensure that future therapies directed against inflammatory Th17 cells do not inadvertently damage the resident gut population.
| S-EPMC6642154 | biostudies-literature
Project description:BACKGROUND: Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). Expression of Th17 pathway-associated genes is mainly studied in colonic disease. The present study assessed the mRNA expression levels of Th17 effector cytokines (IL17A, IL17F, IL21, IL22 and IL26) and genes involved in differentiation (IL6, IL1B, TGFB1, IL23A and STAT3) and recruitment of Th17 cells (CCR6 and CCL20) by quantitative real-time PCR analysis of colonic and ileal biopsies from 22 healthy control subjects, 26 patients with Crohn's disease (CD) and 12 patients with ulcerative colitis (UC). Inflammation was quantified by measuring expression of the inflammatory mediators IL8 and TNF. RESULTS: Evaluation of mRNA expression levels in colonic and ileal control samples revealed that TNF, TGFB1, STAT3 and CCR6 were expressed at higher levels in the ileum than in the colon. Expression of all the Th17 pathway-associated genes was increased in inflamed colonic samples. The increased expression of these genes was predominantly observed in samples from UC patients and was associated with more intense inflammation. Although increased expression of IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged. CONCLUSIONS: Our findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.
| S-EPMC3016394 | biostudies-literature
Project description:Macrophages play a key role in orchestrating the host immune response toward invading organisms or non-self molecules in the oral mucosa. Three-dimensional (3D) oral mucosal equivalents (OME) containing oral fibroblasts and keratinocytes are used extensively to mimic the human oral mucosa where they have been employed to examine innate immune responses to both bacterial and fungal pathogens as well as to biomaterials. Although the presence of immune cells is critical in generating an immune response, very few studies have incorporated leukocytes into OME, and to date, none have contained primary human macrophages. In this study, we report the generation of an immunocompetent OME to investigate immune responses toward bacterial challenge. Primary human monocyte-derived macrophages (MDM) were as responsive to bacterial lipopolysaccharide (LPS) challenge when cultured within a 3D hydrogel in terms of proinflammatory cytokine (IL-6, CXCL8, and TNF-α) gene expression and protein secretion compared with culture as two-dimensional monolayers. MDM were incorporated into a type 1 collagen hydrogel along with oral fibroblasts and the apical surface seeded with oral keratinocytes to generate an MDM-containing OME. Full-thickness MDM-OME displayed a stratified squamous epithelium and a fibroblast-populated connective tissue containing CD68-positive MDM that could be readily isolated to a single-cell population for further analysis by collagenase treatment followed by flow cytometry. When stimulated with LPS, MDM-OME responded with increased proinflammatory cytokine secretion, most notably for TNF-α that increased 12-fold when compared with OME alone. Moreover, this proinflammatory response was inhibited by pretreatment with dexamethasone, showing that MDM-OME are also amenable to drug treatment. Dual-labeled immunofluorescence confocal microscopy revealed that MDM were the sole source of TNF-α production within MDM-OME. These data show functional activity of MDM-OME and illustrate their usefulness for investigations aimed at monitoring the immune response of the oral mucosa to pathogens, biomaterials, and for tissue toxicity and anti-inflammatory drug delivery studies. Impact statement Three-dimensional in vitro models of the oral mucosa have been used extensively to investigate the host response to pathogens, but, to date, few have contained primary leukocytes. In this report, we describe the successful incorporation of primary human macrophages into oral mucosal equivalents (OME). These macrophage-containing models were histologically similar to the oral mucosa and immunoresponsive to bacterial lipopolysaccharides by upregulation of key proinflammatory markers. These advanced OME will significantly aid research into host-pathogen interaction, biomaterial toxicity, and drug delivery studies where the presence of an immune cell component is critical to better represent host oral tissue.
| S-EPMC8403184 | biostudies-literature
Project description:Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both T helper type 1 (Th1) and Th17 responses, and considerable evidence implicates interleukin (IL)-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relative contribution(s) of Th1, Th17, and innate IL-17-producing cells in OPC have not been clearly defined. Here, we sought to determine the nature and function of adaptive T-cell responses to OPC, using a new recall infection model. Mice subjected to infection and re-challenge with Candida mounted a robust and stable antigen-specific IL-17 response in CD4+ but not CD8+ T cells. There was little evidence for Th1 or Th1/Th17 responses. The Th17 response promoted accelerated fungal clearance, and Th17 cells could confer protection in Rag1-/- mice upon adoptive transfer. Surprisingly, CD4 deficiency did not cause OPC but was instead associated with compensatory IL-17 production by Tc17 and CD3+CD4-CD8- cells. Therefore, classic CD4+Th17 cells protect from OPC but can be compensated by other IL-17-producing cells in CD4-deficient hosts.
| S-EPMC3608691 | biostudies-literature