Specific Microbiota-Induced Intestinal Th17 Differentiation Requires MHC Class II but Not GALT and Mesenteric Lymph Nodes

Geem, Duke; Medina-Contreras, Óscar; McBride, Michelle; Newberry, Rodney D.; Koni, Pandelakis A.; Denning, Timothy L.

doi:10.4049/jimmunol.1303167

Cited by 46 publications

(43 citation statements)

References 43 publications

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“…The majority of these cells are specific for SFB-derived antigens, although there are conflicting data regarding whether recognition of cognate antigen is required for their differentiation (80)(81)(82)(83). SFB colonization also induces development of secondary and tertiary lymphoid structures in the intestine, and the development of SFB-specific Th17 cells requires such organized structures (84).…”

Section: Il-23 and Autoimmunitymentioning

confidence: 99%

“…However, several studies have suggested an important role for intestinal APCs in promoting the differentiation of microbiota-dependent intestinal Th17 cells via both antigen-dependent and -independent mechanisms (75,(79)(80)(81). Intestinal Th17 cells show a substantial degree of reactivity to SFB-derived antigens and fail to develop in the absence of MHC class II on CD11c + cells (80,81,83). ATP derived from lumenal microbes specifically induces upregulation of IL-23p19, IL-6, and TGF-β-activating integrins in a CD70 hi CD11c lo population uniquely present in the lamina propria that can support the differentiation of Th17 cells in vitro (75).…”

Section: Il-23 and Autoimmunitymentioning

confidence: 99%

See 1 more Smart Citation

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Burkett¹,

Hörste²,

Kuchroo³

2015

J. Clin. Invest.

204

137

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R e v i e w S e R i e S : A u t o i m m u n i t y2 2 1 2 jci.org Volume 125 Number 6 June 2015Murine Th17 differentiation can also be induced in the absence of TGF-β1 signaling, via the combination either of IL-1β, IL-6, and IL-23 or of 42). These TGF-β1-independent Th17 cells can efficiently induce autoimmune tissue inflammation upon adoptive transfer, a trait that led to them being termed "pathogenic" Th17 cells. Additionally, they possess a gene expression profile distinct from that of "nonpathogenic" Th17 cells, which are differentiated with TGF-β1 and IL-6. These observations have led to two competing hypotheses. The first posits that IL-23 cements Th17 lineage commitment such that Th17 cells induced with TGF-β1 and IL-6 are insufficiently committed to the lineage and cannot induce autoimmune tissue inflammation. The second suggests that there are distinct subtypes of Th17 cells whose differentiation is dependent on distinct combinations of cytokines. The latter hypothesis is supported by the finding that pathogenic Th17 cells express higher levels of several Th1 lineage-associated transcripts, such as the transcription factor T-bet and IFN-γ, and have been shown to be derived from IL-17 single producers by fate mapping experiments (43,44). Similarly, an important feature of human Th17 cells, as well as those isolated from inflamed tissues in mouse models of Th17-mediated disease, is that they coproduce IL-17 with other cytokines, leading to distinct functional roles (45)(46)(47). For instance, human Th17 cells that produce both IL-10 and IL-17 preferentially respond to Staphylococcus aureus, while those that produce both IL-17 and IFN-γ recognize Candida albicans, suggesting that distinct pathogens induce distinct subtypes of Th17 cells (40). IL-17/IFN-γ coproducers have been ascribed pathogenic functions in the CNS during EAE; however, it has been difficult to reliably differentiate such cells in vitro. Repeated rounds of in vitro culture in the presence of either Th1-inducing cytokines or IL-23 can induce IL-17/IFN-γ coproducers, albeit at moderate percentages. The transcription factors T-bet, RUNX1, and RUNX3 appear to be important in the acquisition of this phenotype (48,49).Large-scale transcriptional analysis of Th17 differentiation at very high temporal resolution has begun to elucidate the molecular networks that control this process, and is a promising approach to the identification of novel regulatory molecules that control pathogenic Th17 differentiation (50, 51). In fact, Th17 development is controlled induction of this lineage. The combination of TGF-β1 and IL-6 efficiently induces IL-17-producing murine T cells in vitro and highlights the reciprocal relationship between induced Tregs, which are generated by TGF-β1 alone, and Th17 cells (19,20). A series of studies demonstrated that IL-21, a γ c -dependent cytokine, could promote the differentiation of Th17 cells (21-23). In combination with TGF-β, IL-21 induces IL-17 production from naive Th cells and promotes the expression of both RORγt, th...

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Section: Il-23 and Autoimmunitymentioning

confidence: 99%

Section: Il-23 and Autoimmunitymentioning

confidence: 99%

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Burkett¹,

Hörste²,

Kuchroo³

2015

J. Clin. Invest.

204

137

View full text Add to dashboard Cite

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“…SFB genes related to colonization and immune regulation could be important for this process, and some SFB peptides have been found to promote Th17 cell differentiation (11). Intestinal dendritic cells and major histocompatibility complex (MHC) class II cells also take part in this process (4,12), although the antigen molecules and mechanisms for initial Th17 cell differentiation are still unresolved. Mechanisms that are involved in SFB regulation of the T cell response and IgA secretion need to be investigated further.…”

mentioning

confidence: 99%

Host Specificity of Flagellins from Segmented Filamentous Bacteria Affects Their Patterns of Interaction with Mouse Ileal Mucosal Proteins

Chen

Yin

Wang

et al. 2017

Appl Environ Microbiol

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Segmented filamentous bacteria (SFB) are known modulators of the mammalian immune system. Currently, the technology for investigating SFB culture in vitro is immature, and as a result, the mechanisms of SFB colonization and immune regulation are not yet fully elucidated. In this study, we investigated the gene diversity and host specificity of SFB flagellin genes. The fliC1 and fliC2 genes are relatively conserved, while the fliC3 and fliC4 genes are more variable, especially at the central and C-terminal regions. Host specificity analysis demonstrated that the fliC1 genes do not cluster together based on the host organism, whereas the fliC3 and fliC4 genes were host specific at the nucleotide and deduced amino acid levels. SFB flagellin protein expression in the ileum mucosa and cecal contents was detected by using fluorescence in situ hybridization (FISH) combined with immunohistochemical (IHC) analysis, immunoblotting, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the purified SFB FliC3 protein originating from both mouse and rat was able to activate Toll-like receptor 5 (TLR5)-linked NF-B signaling, no host specificity was observed. Interestingly, the patterns of interaction with mouse ileum mucosal proteins were different for mouse FliC3 (mFliC3) and rat FliC3 (rFliC3). Gene Ontology (GO) and KEGG analyses indicated that more adherence-related proteins interacted with mFliC3, while more lysosome-and proteolysis-related proteins interacted with rFliC3. In vitro degradation experiments indicated that the stability of rFliC3 was lower than that of mFliC3 when they were incubated with mouse ileum mucosal proteins. In summary, the gene diversity and host specificity of SFB flagellin genes were investigated, and SFB flagellin expression was detected in gut samples.IMPORTANCE Since SFB genomes contain only one copy of each FliC gene, the diversity of FliC is representative of SFB strain diversity. Currently, little is known regarding the diversity and specificity of members of the group of SFB. The work presented herein demonstrates that select SFB strains, exhibiting unique FliC patterns, are present in a variety of mammalian hosts. SFB fliC genes were found to interact with a number of unique targets, providing further evidence for SFB host selection. Together, this work represents a major advancement in identifying SFB and delineating how members of the group of SFB interact with the host. Future examination of FliC genes will likely enhance our knowledge of intestinal colonization by the gut microbiota.KEYWORDS segmented filamentous bacteria, flagellin, host specificity, gene diversity, ileum mucosal proteins

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“…The T helper 17 (T h 17) cells play a potential role in protecting the pathogens and inducing inflammation and autoimmunity (25)(26)(27), whereas regulatory T cells prevent inflammation and confer immune tolerance (25,28,29). Recent studies have reported that segmented filamentous bacteria played a crucial role in inducing T h 17 cells localized in lamina propria of intestinal mucosa and lenfoid tissue (24,30). Besides, increased IL-17 secreting T cells have also been observed in newly started type-1 diabetes (31).…”

mentioning

confidence: 99%

“…In murine models with type-1 diabetes, the intestinal flora was shown to alter in favor of bacteroids in comparison to healthy controls (18,19). The modified composition of microflora apparently affects T cells especially interleukin-17 (IL-17) producing T helper (T h ) and regulatory T cells (20)(21)(22)(23)(24). The T helper 17 (T h 17) cells play a potential role in protecting the pathogens and inducing inflammation and autoimmunity (25)(26)(27), whereas regulatory T cells prevent inflammation and confer immune tolerance (25,28,29).…”

mentioning

confidence: 99%

The Role of Gluten-free Diet and Intestinal Microbiota on Glycemic Control and Diabetes Development

Çakır¹,

Ataoğlu²,

Yenigün³

2017

Turk J Endocrinol Metab

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Gluten is an important ingredient of wheat protein, as about 90% of the total protein content is gluten. Besides, it is also present in barley, oat, and rye (1-3), and these gluten-rich cereals constitute the major part of our diet. Gluten is a water-insoluble protein and consists of two major fractions, i.e., gliadin and glutenin. Gliadin is the aqueous alcohol-soluble fraction, and its firm peptide configuration renders it resistant to lytic enzyme system in the gastrointestinal tract and this distinct resistance is considered to trigger A gluten-free diet offers immense health benets in certain autoimmune diseases including dermatitis herpetiformis, rheumatoid arthritis, and neurologic disorders; besides its therapeutic potential has also been documented in other conditions such as diabetes mellitus, HIVassociated enteropathy, and celiac disease. In animal models, a gluten-free diet has been associated with the reduced auto-inammatory process, altered inammatory cytokine response as well as intestinal microbiota leading to lower the incidence of diabetes. The acidic environment has also been shown to affect the gut microbiota resulting in reduced incidence and delayed onset of diabetes in genetically predisposed individuals. In the current article, it has been proposed that intestinal microbiota play a major role in stimulating an immunological response; and the acidic environment affects the gut microbiota, and thus improves the immunological milieu. Gluten-free diets positively boost the immunological response in animal models and combat with autoimmune diseases in human beings by affecting the gut ora. The association between gluten-free diet, gut ora, immunological response, and environment may play a decisive role in plummeting the advancement of diabetes.Keywords: Gluten-free diet, cytokines, intestinal microbiota, acidic environment, diabetes mellitus Glutensiz diyet, dermatit herpetiformis, romatoid artrit ve nörolojik bozukluklar gibi otoimmün hastalıklarda sağlığa faydalı etkiler sunmaktadır; ayrıca diabetes mellitus, HIV ile ilişkili enteropati ve çölyak hastalığında da tedavideki olumlu etkinliği bildirilmiştir. Hayvan modellerinde, glutensiz diyet otoinamatuvar süreçde baskılanma ve değişen inamatuvar sitokin yanıtı ile diyabet insidansında azaltmaya yol açan bağırsak mikrobiyota değişimi ile ilişkilendirilmiştir. Asidik ortamın bağırsak mikrobiyota ortamını etkilediği ve genetik olarak yatkın bireylerde diyabet insidansı azalttığı ve diyabetin başlamasını geciktirdiği gösterilmiştir. Bu makale ile bağırsak mikrobiyotasının immünolojik cevabı uyarmada önemli bir rol oynadığı sunulmaktadır; ve asidik ortam bağırsak mikrobiyotasını etkileyerek immünolojik ortamı geliştirir. Glutensiz diyet, bağırsak orasını etkileyerek hayvan modellerinde immünolojik yanıtta ve insanda otoimmün hastalıklarla mücadelede olumlu yönde destek sağlamaktadır. Glutensiz diyet, bağırsak orası, immünolojik tepki ve immünolojik ortam arasındaki ilişki, diyabetin ilerlemesini azaltmada belirleyici rol oynayabilir.

show abstract

Specific Microbiota-Induced Intestinal Th17 Differentiation Requires MHC Class II but Not GALT and Mesenteric Lymph Nodes

Cited by 46 publications

References 43 publications

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Host Specificity of Flagellins from Segmented Filamentous Bacteria Affects Their Patterns of Interaction with Mouse Ileal Mucosal Proteins

The Role of Gluten-free Diet and Intestinal Microbiota on Glycemic Control and Diabetes Development

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