Intestinal CD4-CD8αβ-TCRαβ+ T cells function as tolerogenic antigen presenting cells in mice
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ABSTRACT:
PROVIDER: PRJNA1268409 | ENA |
REPOSITORIES: ENA
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Project description:To distinguish harmless from harmful antigens (Ag), anatomic, cellular and molecular mechanisms operate in the intestinal tract to acquire, process, present and interpret luminal Ags. The intestinal mucosa is populated by many T cell types in the intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) populations, including double negative CD4-CD8αβ-TCRαβ+ T (double-negative T/DNT) cells. Here we show that murine DNT cells in the small intestine reach across the epithelial barrier to capture luminal Ags. A sizeable fraction of DNT cells in Peyer’s patches and mesenteric lymph nodes express MHC-II, but little or no classical co-stimulatory molecules. Indeed, DNT cells acquire, process and present antigenic proteins to tolerize Ag-specific CD4+ T cells. Conditional genetic ablation of MHC-II in T cells disable this tolerogenic function and rendered mutant mice hypersusceptible to intestinal inflammation. Intriguingly, intestinal T cells in patients with Crohn’s disease express lower levels of HLA-DR than those from controls. Our findings thus suggest that MHC-II+ DNT cells may regulate intestinal immune homeostasis and their dysfunction may contribute to the pathogenesis of inflammatory bowel disease.
2025-07-09 | GSE298133 | GEO
Project description:Immature dendritic cells (DCs) that are incubated with TLR-ligands during in vitro differentiation develop a tolerogenic phenotype. Especially an early encounter of isolated monocytes with the Toll-like receptor 7/8 ligand R848 mediates a switch of pro-inflammatory to immunosupressive properties. We were strongly interested in the identification of factors that are involved in the differentiation of these tolerogenic cells, thus we performed gene expression analysis.
2017-05-03 | GSE98480 | GEO
Project description:Antigen-presenting cells are responsible for the initiation of T cell responses and critically shape tolerogenic or inflammatory immune responses to the gut microbiota. Here, we employed the pathobiont Helicobacter hepaticus, and performed single-cell RNA sequencing for all antigen-presenting cells in the large intestine in various contexts.
2025-06-18 | GSE254246 | GEO
Project description:CD8αβ+ intraepithelial lymphocytes (IELs) are a subset of “effector-memory-like” T cells scattered along the intestinal epithelium. To investigate if CD8αβ+ IEL can function in ways other than the conventional cytotoxic effect of CD8αβ+ T cells,CD8αβ+ IELs were compared with CD8αβ+ splenocytes (SPL) by RNA-seq. We used microarrays to identify new functions of CD8αβ+ IELs .
2018-05-30 | GSE105061 | GEO
Project description:The human immune system evolves gradually from the embryo to adult, continuously adapting to the ever-changing environment of the human body. The ability of our immune system to sense external cues and adapt as we develop is as important in the early tolerogenic environment of the fetus, as it is in the constantly pathogen-challenged adult. Dendritic cells (DC), professional antigen sensing and presenting cells, play a crucial role in such processes as sentinels of the immune system, initiating and regulating immune responses. We have previously characterised CD14+ DC, CD1c+DC and CD141+DC subset by flow cytometry and microarray transcriptome analysis in adult mucosal tissues, and have described their superior abilities to either induce IL-17 responses or to cross-present external antigens respectively. However, the role of such DC subsets in the tolerogenic environment of the fetus remains undefined, prompting us to investigate the ontogeny and functional significance of human fetal DCs.
2017-06-28 | GSE85304 | GEO
Project description:Assessing the gene expression repertoire of antigen presenting dendritic cells Keywords: other
2004-09-30 | GSE702 | GEO
Project description:Gene expression signatures for CD8αβ+ intraepithelial lymphocytes and CD8αβ+ splenocytes.
| PRJNA414538 | ENA
Project description:Regulatory T cell (Treg)-based therapeutics are receiving increased attention for their potential to treat autoimmune disease and prevent transplant rejection. Adoptively transferred Tregs have shown promise in early clinical trials, but cell-based therapies are expensive and complex to implement, and "off-the-shelf" alternatives are needed. Here, we investigate the potential of artificial antigen presenting cells (aAPCs) fabricated from a blend of negatively charged biodegradable polymer (poly(lactic-co-glycolic acid), PLGA) and cationic biodegradable polymer (poly(beta-amino ester), PBAE) with incorporation of extracellular protein signals 1 and 2 and a soluble released signal 3 to convert naïve T cells to induced Foxp3+ Treg-like suppressor cells (iTregs) both in vitro and in vivo in a biomimetic manner. The addition of PBAE to the aAPC core increased the conjugation efficiency of signal proteins to the particle surface and resulted in enhanced ability to bind to naïve T cells and induce iTregs with potent suppressive function. Furthermore, PLGA/PBAE tolerogenic aAPCs (TolAPCs) supported the loading and sustained release of signal 3 cytokine TGF-β. A single dose of TolAPCs administered intravenously to C57BL/6 J mice resulted in an increased percentage of Foxp3+ cells in the lymph nodes. Thus, PLGA/PBAE TolAPCs show potential as an "off-the-shelf" biomimetic material for tolerance induction. STATEMENT OF SIGNIFICANCE: Regulatory T cells (Tregs) are promising for basic research and translational medicine as they can induce tolerance and have the potential to treat autoimmune diseases such as type 1 diabetes and multiple sclerosis. As cell-based therapies are expensive and difficult to manufacture and implement, non-cellular methods of engineering endogenous Tregs are needed. The research reported here describes a new type of biomimetic particle, tolerogenic artificial antigen presenting cells (TolAPCs) fabricated from a blend of negatively charged biodegradable polymer, poly(lactic-co-glycolic acid), and positively charged biodegradable polymer, poly(beta-amino ester), along with key biomolecular signals: extracellularly presented protein signals 1 and 2 and a soluble released signal 3. These TolAPCs bind to naïve T cells and induce Foxp3+ Treg-like suppressor cells with potent suppressive function. In both in vitro and in vivo studies, it is shown that this non-cellular approach is useful to induce tolerance.
| S-EPMC7365762 | biostudies-literature
Project description:Transcriptional profiles of four different myeloid antigen presenting cell (APC) subsets (BDCA-1+ circulating myeloid dendritic cells, CD14+ monocytes, and in vitro generated immature and mature monocyte-derived dendritic cells) were used for comprehensive transcriptome analysis. Based on the gene expression profiling data, a quantitative relationship between myeloid APC in functionally related gene spaces was established. Keywords = myeloid antigen presenting cells Keywords = dendritic cell subsets Keywords: repeat sample
2017-12-21 | GSE2215 | GEO
Project description:The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens to CD4+ T cells and inducing their differentiation into regulatory (pTreg) or inflammatory (Th) subsets. Here, we used LIPSTIC to identify APCs that presented dietary antigens under tolerizing and inflammatory conditions. We show that helminth infections disrupted tolerance proportionally to the reduction in ratio between tolerogenic, including migratory cDC1s and Rorγt+ APCs, and inflammatory APCs, represented primarily by cDC2 subsets. However, the inflammatory subset of cDC2s expanded by helminth infection did not present dietary antigens, thus avoiding diet-specific TH2 cell differentiation. Our data uncover cellular mechanisms by which tolerance to food is induced and can be disrupted by infection.
2024-12-19 | GSE281286 | GEO