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Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE188322 | GEO | 2021/11/05

REPOSITORIES: GEO

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Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

Project description:Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

| PRJNA778252 | ENA

Single-cell clonotype tracing identifies a stem-like intestinal Th17 population that gives rise to pathogenic effector T cells during autoimmunity

Project description:While intestinal Th17 cells are critical for maintaining tissue homeostasis, recent studies in both humans and mice have implicated their roles in the development of extra-intestinal autoimmune diseases such as multiple sclerosis. However, the mechanisms by which tissue Th17 cells mediate these dichotomous functions remain unknown. Here, we characterized the heterogeneity, plasticity, and migratory phenotypes of tissue Th17 cells in vivo by combining fate mapping with single-cell RNA sequencing to profile the transcriptomes and TCR clonotypes of over 84,000 Th17 cells at homeostasis and during CNS autoimmune inflammation. Inter- and intra-organ single-cell analyses revealed a homeostatic, stem-like TCF1+ IL-17+ SLAMF6+ population that traffics to the intestine where it is maintained by the microbiota, providing a ready-reservoir for the IL-23-driven generation of encephalitogenic GM-CSF+ IFNγ+ CXCR6+ T cells. Our study defines a direct relationship in vivo between IL-17+ non-pathogenic and GM-CSF+ and IFNγ+ pathogenic Th17 populations and provides, for the first time, a mechanism by which homeostatic intestinal Th17 cells direct extra-intestinal autoimmune disease.

2021-11-05 | GSE188320 | GEO

Autoimmunity and infection give rise to distict inflammatory Th17 subsets

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

2023-06-13 | GSE234594 | GEO

Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection.

Project description: Not available

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Autoimmunity and infection give rise to distict inflammatory Th17 subsets [bulk RNA-seq]

Project description:Th17 cells are a heterogeneous population that is critical for tissue homeostasis and inflammation during clearance of infections and autoimmunity. Despite substantial efforts distinguishing homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells is poorly understood. In this study, we show that the inflammatory Th17 engaged in autoimmune colitis and those involved in infection-induced colitis are two distinguishable populations illustrated by their distinct responses to a pharmacological molecule, clofazimine (CLF). Distinct from existing Th17 inhibitors, CLF selectively inhibits pro-autoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells through restricting Aldh1l2expression. Using bulk RNA sequencing, we explored transcriptional response to CLF on in vitro differentiated inflammatory and homeostatic Th17 cells. Notably, we identified a unique suppression in the transcription of signature inflammatory genes in Th17 cells with a marginal effect on those elicited by infection.

2023-06-13 | GSE234593 | GEO

Hematopoietic stem cells give rise to osteo-chondrogenic cells.

Project description: Not available

| S-EPMC3521579 | biostudies-literature

Autoimmunity and infection give rise to distict inflammatory Th17 subsets [single-cell RNA-seq]

Project description:Th17 cells are a heterogeneous population that is critical for tissue homeostasis and inflammation during clearance of infections and autoimmunity. Despite substantial efforts distinguishing homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells is poorly understood. In this study, we show that the inflammatory Th17 engaged in autoimmune colitis and those involved in infection-induced colitis are two distinguishable populations illustrated by their distinct responses to a pharmacological molecule, clofazimine (CLF). Distinct from existing Th17 inhibitors, CLF selectively inhibits pro-autoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells through restricting Aldh1l2expression. Using single-cell RNA sequencing, we explored inflammatory Th17 transcriptional response to CLF from the colonic tissue of mice during autoimmune colitis and Citrobacter rodentiuminfection using Rorc gfp/+ reportor mice. Notably, we identified a unique suppression in the transcription of signature inflammatory genes in Th17 cells from autoimmune colitis with a marginal effect on those elicited by infection. Additionally, we illustrate with these data that the transcriptionally programming of pro-autoimmune Th17 cells are, indeed, unique compared to infection-elicited Th17 cells. Finally, we analyzed the impact of CLF on human inflammatory Th17 cells from the inflammed colon of a patient with IBD.

2023-06-13 | GSE234592 | GEO

Single-cell clonotype tracing identifies a stem-like intestinal Th17 population that gives rise to pathogenic effector T cells during autoimmunity

Project description:Single-cell clonotype tracing identifies a stem-like intestinal Th17 population that gives rise to pathogenic effector T cells during autoimmunity

| PRJNA778255 | ENA

Effector TH17 cells give rise to long-lived TRM cells that are essential for an immediate response against bacterial infection

Project description:Mucosal barrier surfaces serve as the critical first line of defense separating our bodies from the plethora of pathogenic microorganisms that inhabit our environment. Adaptive immunity provides life-long protection through the generation of a central and effector memory T-cell pool, memory B cells and the recently described population of tissue resident memory cells (TRM). The cellular origin of TRM CD4 cells is unknown and the contribution of this CD4 memory population to host defense still remains elusive. By using IL-17A tracking-fate-mouse models we found that a significant fraction of the CD4 TRM cells derive from IL-17A producing effector (TH17) cells following primary immunization. Maintenance of these resting exTH17 TRM cells is mediated by IL-7, produced by lymphatic endothelial cells. During a memory response, we show that neither antibodies, nor gd T cells, nor circulatory memory T cells are sufficient for the rapid host defense required to eliminate the pathogen. Using parabiosis and depletion studies, we demonstrated that CD4 exTH17 TRM cells play an important role in respiratory defense and bacterial clearance. Upon infection, exTH17 TRM cells rapidly produce IL-17A and IFN-γ to promote neutrophil infiltration and bacterial clearance. These studies delineate the origin, function and importance of airway CD4 TRM cells during bacterial infection, offering novel strategies for targeted vaccine design, which is especially imperative for those pathogens that are resistant to antibiotic treatment.

2019-04-30 | GSE130446 | GEO

Effector TH17 cells give rise to long-lived TRM cells that are essential for an immediate response against bacterial infection

2019-05-21 | GSE131450 | GEO

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