Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes

Sano, Teruyuki; Kageyama, Takahiro; Fang, Victoria; Kedmi, Ranit; Martinez, Carlos Serafin; Talbot, Jhimmy; Chen, Alessandra; Cabrera, Ivan; Gorshko, Oleksandra; Kurakake, Reina; Yang, Yi; Ng, Charles; Schwab, Susan R.; Littman, Dan R.

doi:10.1016/j.celrep.2021.109608

Cited by 24 publications

(19 citation statements)

References 62 publications

(94 reference statements)

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“…IL-6 is a pleiotropic cytokine able to prevent epithelial apoptosis during prolonged inflammation and produced by intraepithelial lymphocytes at the onset of an inflammatory injury for intestinal epithelial proliferation and wound repairs [ 39 ]. Additionally, IL-6 were moderate expression in submucosal ILFs, where IL-6 was an essential cytokine for early RORγt expressed by microbe-dependent Th17 cells and led to their differentiation [ 40 ]. CD4 + T cells in the LGH group were more widely distributed than in the control group.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Mucosal Barrier Improvement with Prebiotics: Histological Evaluation of Longish Glucomannan Hydrolysates-Induced Innate T Lymphocyte Activities in Mice

et al. 2022

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Use of prebiotics is a growing topic in healthcare. A lightweight molecule and water-soluble fiber ingredient, longish glucomannan hydrolysates (LGH), has been developed to improve the intestinal mucosal barrier and confer gut health benefits. This study aims to investigate the implications of continuous LGH intervening in intestinal epithelium integrity and protective immunity against chemical dextran sodium sulfate (DSS)-induced colitis. Twelve male BALB/c mice were randomly arranged into four groups. The LGH/DSS group had results in bodyweight variance, epithelial cell density, and aberrancy score as good as the LGH group, and both were equivalent to the control group. LGH consumption effectively protects the distal intestinal epithelium by activating innate T lymphocytes. Meanwhile, T-cell subsets in subepithelial interspersion take a bystander role in these microenvironmental alterations. Under this stress, the cluster of differentiation 3 (CD3)+ T cells infiltrate the epithelium, while CD4+ T cells inversely appear in submucosal large lymphoid aggregates/isolated lymphoid follicles (ILFs) in which significant CD3+, CD4+, and CD8+ T-cell populations agglomerate. Moreover, forkhead box P3 (Foxp3) and interleukin 17 (IL-17) are observed in these ILFs. Agglomerated CD4+ T-cell lineages may have roles with proinflammatory T helper 17 cells and anti-inflammatory regulatory T cells in balancing responses to intraluminal antigens. Collectively, LGH administration may function in immune modulation to protect against DSS-induced inflammation.

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Section: Discussionmentioning

confidence: 99%

Intestinal Mucosal Barrier Improvement with Prebiotics: Histological Evaluation of Longish Glucomannan Hydrolysates-Induced Innate T Lymphocyte Activities in Mice

et al. 2022

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“…The reactions initiated by commensal bacteria influence the antigen-specific adaptive immunity. Th17 lymphocytes (T-helper-17), a type of CD4 + T-helper cells, play a key role in coordinating the inflammatory immune response that provides protection against pathogens [38]. Th17 lymphocytes support actions against fungal and bacterial pathogens in the mucous membranes of the respiratory and digestive systems [38,39].…”

Section: The Influence Of Microbiota On the Immune Systemmentioning

confidence: 99%

“…Th17 lymphocytes (T-helper-17), a type of CD4 + T-helper cells, play a key role in coordinating the inflammatory immune response that provides protection against pathogens [38]. Th17 lymphocytes support actions against fungal and bacterial pathogens in the mucous membranes of the respiratory and digestive systems [38,39]. They limit side effects and ensure specific tolerance to food and bacterial antigens.…”

Section: The Influence Of Microbiota On the Immune Systemmentioning

confidence: 99%

The Role of Nutritional Factors in the Modulation of the Composition of the Gut Microbiota in People with Autoimmune Diabetes

et al. 2022

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Type 1 diabetes mellitus (T1DM) is a disease marked by oxidative stress, chronic inflammation, and the presence of autoantibodies. The gut microbiota has been shown to be involved in the alleviation of oxidative stress and inflammation as well as strengthening immunity, thus its’ possible involvement in the pathogenesis of T1DM has been highlighted. The goal of the present study is to analyze information on the relationship between the structure of the intestinal microbiome and the occurrence of T1DM. The modification of the intestinal microbiota can increase the proportion of SCFA-producing bacteria, which could in turn be effective in the prevention and/or treatment of T1DM. The increased daily intake of soluble and non-soluble fibers, as well as the inclusion of pro-biotics, prebiotics, herbs, spices, and teas that are sources of phytobiotics, in the diet, could be important in improving the composition and activity of the microbiota and thus in the prevention of metabolic disorders. Understanding how the microbiota interacts with immune cells to create immune tolerance could enable the development of new therapeutic strategies for T1DM and improve the quality of life of people with T1DM.

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“…The gastrointestinal microbiota has further been reported to exhibit immunomodulatory activity capable of activating innate and adaptive immunity 12,13 . While few commensal bacteria have been confirmed to induce antigen-specific T cell responses, commensal-specific T cells are nonetheless thought to provide diverse T cell receptor (TCR) repertoires that supply a variety of T cell pools 14 , particularly given that these commensal-specific T cells can enter systemic circulation 15,16 . Some commensals contribute to not only the generation of protective and homeostatic immunity but also the onset and severity of several autoimmune diseases 17 .…”

Section: Mainmentioning

confidence: 99%

“…When naïve CD4 T cells are adaptively transferred from these SFB TCR Tg mice into wild-type (WT) C57BL/6 hosts, they differentiate into Th17 cells in the gut-draining mesenteric lymph nodes (mLNs) in response to SFB 30 . A majority of these expanded SFB-specific CD4 T cells are maintained in the intestines where the commensals they recognize are located 16 , yet a subset of these cells are detectable in distal tissues including the spleen and lungs 16,31 . As such, SFB TCR Tg mice represent an ideal tool for use when exploring the relationships between commensal-derived antigen specificity and the pathogenesis of tissue inflammation.…”

Section: Mainmentioning

confidence: 99%

Commensal-specific CD4 T cells promote inflammation in the central nervous system via molecular mimicry

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Cabrera

Ochoa-Raya

et al. 2022

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Commensal bacteria are critical regulators of both tissue homeostasis and the development and exacerbation of autoimmunity. However, it remains unclear how the intestinal microbiota contributes to inflammation in tissues such as the central nervous system (CNS) where these microbes are typically absent and whether T cell receptor (TCR) specificity for commensal-derived antigens is important to the development of tissue inflammation-related outcomes. Here, we found that ileum- and cecum-colonizing segmented filamentous bacteria (SFB)-specific T cells (clone TCR7B8) can infiltrate the CNS wherein they can be reactivated and produce high levels of inflammatory cytokines including IFNg, IL-17A, TNFa, and GM-CSF in the absence of regulatory T cells. In contrast, other SFB-specific T cells (clone TCR1A2) recognizing an epitope in which 8/9 amino acids overlap with those recognized by TCR7B8 failed to induce such neuroinflammation. Despite their similar SFB-derived peptide antigen targets, TCR7B8 was found to recognize peptides derived from host proteins including receptor tyrosine-protein kinase ErbB2, trophinin 1, and anaphase-promoting complex subunit 2 in vitro, whereas TCR1A2 did not, indicating that TCR7B8 induces CNS inflammation via molecular mimicry. Immune checkpoint blockade accelerated TCR7B8-mediated CNS inflammation, suggesting a potential cause of immune-related adverse events induced in cancer patients undergoing such treatment. Together, our findings reveal a potential mechanism whereby gut commensal-specific T cells are dysregulated and contribute to extraintestinal inflammation.

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Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes

Cited by 24 publications

References 62 publications

Intestinal Mucosal Barrier Improvement with Prebiotics: Histological Evaluation of Longish Glucomannan Hydrolysates-Induced Innate T Lymphocyte Activities in Mice

Intestinal Mucosal Barrier Improvement with Prebiotics: Histological Evaluation of Longish Glucomannan Hydrolysates-Induced Innate T Lymphocyte Activities in Mice

The Role of Nutritional Factors in the Modulation of the Composition of the Gut Microbiota in People with Autoimmune Diabetes

Commensal-specific CD4 T cells promote inflammation in the central nervous system via molecular mimicry

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