Dataset Information

Gamma-delta T cells modulate the microbiota and fecal micro-RNAs to maintain mucosal tolerance.

ABSTRACT:

Background

Gamma-delta (γδ) T cells are a major cell population in the intestinal mucosa and are key mediators of mucosal tolerance and microbiota composition. Little is known about the mechanisms by which intestinal γδ T cells interact with the gut microbiota to maintain tolerance.

Results

We found that antibiotic treatment impaired oral tolerance and depleted intestinal γδ T cells, suggesting that the gut microbiota is necessary to maintain γδ T cells. We also found that mice deficient for γδ T cells (γδ^-/-) had an altered microbiota composition that led to small intestine (SI) immune dysregulation and impaired tolerance. Accordingly, colonizing WT mice with γδ^-/- microbiota resulted in SI immune dysregulation and loss of tolerance whereas colonizing γδ^-/- mice with WT microbiota normalized mucosal immune responses and restored mucosal tolerance. Moreover, we found that SI γδ T cells shaped the gut microbiota and regulated intestinal homeostasis by secreting the fecal micro-RNA let-7f. Importantly, oral administration of let-7f to γδ^-/- mice rescued mucosal tolerance by promoting the growth of the γδ^-/--microbiota-depleted microbe Ruminococcus gnavus.

Conclusions

Taken together, we demonstrate that γδ T cell-selected microbiota is necessary and sufficient to promote mucosal tolerance, is mediated in part by γδ T cell secretion of fecal micro-RNAs, and is mechanistically linked to restoration of mucosal immune responses. Video Abstract.

SUBMITTER: Rezende RM

PROVIDER: S-EPMC9948450 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Gamma-delta T cells modulate the microbiota and fecal micro-RNAs to maintain mucosal tolerance.

Rezende Rafael M RM Cox Laura M LM Moreira Thais G TG Liu Shirong S Boulenouar Selma S Dhang Fyonn F LeServe Danielle S DS Nakagaki Brenda N BN Lopes Juliana R JR Tatematsu Bruna K BK Lemos Luisa L Mayrink Julia J Lobo Eduardo L C ELC Guo Lydia L Oliveira Marilia G MG Kuhn Chantal C Weiner Howard L HL

Microbiome 20230223 1

<h4>Background</h4>Gamma-delta (γδ) T cells are a major cell population in the intestinal mucosa and are key mediators of mucosal tolerance and microbiota composition. Little is known about the mechanisms by which intestinal γδ T cells interact with the gut microbiota to maintain tolerance.<h4>Results</h4>We found that antibiotic treatment impaired oral tolerance and depleted intestinal γδ T cells, suggesting that the gut microbiota is necessary to maintain γδ T cells. We also found that mice de ...[more]

PMID: 36814316

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Project description:Axial spondyloarthritis (axSpA) is an inflammatory arthritis involving the spine and the sacroiliac joint with extra-articular manifestations in the eye, gut, and skin. The intestinal microbiota has been implicated as a central environmental component in the pathogenesis of various types of spondyloarthritis including axSpA. Additionally, alterations in the oral microbiota have been shown in various rheumatological conditions, such as rheumatoid arthritis (RA). Therefore, the aim of this study was to investigate whether axSpA patients have an altered immunoglobulin A (IgA) response in the gut and oral microbial communities. We performed 16S rRNA gene (16S) sequencing on IgA positive (IgA+) and IgA negative (IgA-) fractions (IgA-SEQ) from feces (n=17 axSpA; n=14 healthy) and saliva (n=14 axSpA; n=12 healthy), as well as on IgA-unsorted fecal and salivary samples. PICRUSt2 was used to predict microbial metabolic potential in axSpA patients and healthy controls (HCs). IgA-SEQ analyses revealed enrichment of several microbes in the fecal (Akkermansia, Ruminococcaceae, Lachnospira) and salivary (Prevotellaceae, Actinobacillus) microbiome in axSpA patients as compared with HCs. Fecal microbiome from axSpA patients showed a tendency towards increased alpha diversity in IgA+ fraction and decreased diversity in IgA- fraction in comparison with HCs, while the salivary microbiome exhibits a significant decrease in alpha diversity in both IgA+ and IgA- fractions. Increased IgA coating of Clostridiales Family XIII in feces correlated with disease severity. Inferred metagenomic analysis suggests perturbation of metabolites and metabolic pathways for inflammation (oxidative stress, amino acid degradation) and metabolism (propanoate and butanoate) in axSpA patients. Analyses of fecal and salivary microbes from axSpA patients reveal distinct populations of immunoreactive microbes compared to HCs using the IgA-SEQ approach. These bacteria were not identified by comparing their relative abundance alone. Predictive metagenomic analysis revealed perturbation of metabolites/metabolic pathways in axSpA patients. Future studies on these immunoreactive microbes may lead to better understanding of the functional role of IgA in maintaining microbial structure and human health.

Dataset Information

Gamma-delta T cells modulate the microbiota and fecal micro-RNAs to maintain mucosal tolerance.

Background

Results

Conclusions

Publications

Gamma-delta T cells modulate the microbiota and fecal micro-RNAs to maintain mucosal tolerance.

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