Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine

Shaw, Michael H.; Kamada, Nobuhiko; Yun-Gi, Kim; Nuñez, Guillermo Gabriel

doi:10.1084/jem.20111703

Cited by 304 publications

(305 citation statements)

References 24 publications

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“…IL-1b was linked to the promotion of Th17 development in models of autoimmune diseases and bacterial and fungal infections, as well as in inflammatory and steady-state conditions in the intestine (2,3,54,55). In line with this, we show in this study that IFN-g-induced suppression of IL-1b resulted in impaired generation of IL-17-producing cells in vitro.…”

Section: Discussionsupporting

confidence: 83%

Early Inhibition of IL-1β Expression by IFN-γ Is Mediated by Impaired Binding of NF-κB to the IL-1β Promoter but Is Independent of Nitric Oxide

Eigenbrod

Bode

Dalpke

2013

The Journal of Immunology

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The significance of bacterial RNA recognition for initiating innate immune responses against invading pathogens has only recently started to be elucidated. Bacterial RNA is an important trigger of inflammasome activation, resulting in caspase-1–dependent cleavage of pro–IL-1β into the active form. It was reported previously that prolonged treatment with IFN-γ can inhibit IL-1β production at the level of both transcription and Nlrp3 inflammasome activation in an NO-dependent manner. As a result of the delayed kinetics of NO generation after IFN-γ stimulation, these effects were only observed at later time points. We report that IFN-γ suppressed bacterial RNA and LPS induced IL-1β transcription in primary murine macrophages and dendritic cells by an additional, very rapid mechanism that was independent of NO. Costimulation with IFN-γ selectively attenuated binding of NF-κB p65 to the IL-1β promoter, thus representing a novel mechanism of IL-1β inhibition by IFN-γ. Transcriptional silencing was specific for IL-1β because expression of other proinflammatory cytokines, such as TNF, IL-6, and IL-12p40, was not affected. Furthermore, by suppressing IL-1β production, IFN-γ impaired differentiation of Th17 cells and production of neutrophil chemotactic factor CXCL1 in vitro. The findings provide evidence for a rapid immune-modulating effect of IFN-γ independent of NO.

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Section: Discussionsupporting

confidence: 83%

Early Inhibition of IL-1β Expression by IFN-γ Is Mediated by Impaired Binding of NF-κB to the IL-1β Promoter but Is Independent of Nitric Oxide

Eigenbrod

Bode

Dalpke

2013

The Journal of Immunology

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“…Although these results support early in vitro studies (2-4) and one study showing that TGF-β1 was required for the initiation of EAE (14), they are in contrast to in vivo studies that showed that IL-6 is not required for microbiota-induced Th17 cell formation (9) and that TGF-β1 is not required for Th17 differentiation during EAE induction (8). The fact that IL-1β or IL-23 was important for Th17 cell differentiation in the cases where IL-6 or TGF-β1 was not suggests the existence of several independent Th17 cell differentiation pathways (8,9). The IL-6-and TGF-β1-dependent pathway induced by i.n.…”

Section: Discussionsupporting

confidence: 75%

“…infection by Streptococcus pyogenes, and TGF-β1 receptor signaling and IL-6 are involved (6,7). However, Th17 cell formation in the small intestine does not depend on TGF-β1 (8) and requires IL-1β but not IL-6 (9). Additionally, Kuchroo and colleagues reported that although Th17 differentiation was normally dependent on IL-6, it could occur without it through an IL-21-dependent pathway if regulatory T cells were absent (10).…”

mentioning

confidence: 99%

Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b ⁺ dendritic cells

Linehan

Dileepan

Kashem

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Intranasal (i.n.) infections preferentially generate Th17 cells. We explored the basis for this anatomic preference by tracking polyclonal CD4 + T cells specific for an MHC class II-bound peptide from the mucosal pathogen Streptococcus pyogenes. S. pyogenes MHC class II-bound peptide-specific CD4 + T cells were first activated in the cervical lymph nodes following i.n. inoculation and then differentiated into Th17 cells. S. pyogenes-induced Th17 formation depended on TGF-β1 from dendritic cells and IL-6 from a CD301b + dendritic cell subset located in the cervical lymph nodes but not the spleen. Thus, the tendency of i.n. infection to induce Th17 cells is related to cytokine production by specialized dendritic cells that drain this site.Th17 | CD301b+ | dendritic cells | Streptococcus pyogenes

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“…For example, IL-1b increases the cell response to anti-CD3 stimulation and encourages maturation toward IL-17A production in CD161 + T cells (25). Similarly, conventional CD4 + T cells with a Th17 signature possess extended functional plasticity, and IL-7 (29,30) or a combination of IL-1b and IL-23 (31,32) may reduce the T cell-activation threshold and positively influence differentiation toward Th17 cells. Because Liv-MAIT cells produced high quantities of IL-17A only after mitogen stimulation, we tested whether inflammatory cytokines influence the maturation and responsiveness of Liv-MAIT cells to TCR-mediated stimulation.…”

Section: Il-7 Licenses Mait Cells To Produce Large Quantities Of Ifn-mentioning

confidence: 99%

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

Tang

Tan

et al. 2013

The Journal of Immunology

311

408

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Human mucosal-associated invariant T (MAIT) cells are a T cell population characterized by the expression of a semi-invariant TCR capable of recognizing bacterial products in the context of MR1. MAIT cells are enriched in the human liver, which is constantly exposed to bacterial products from the intestine. Whether this specific parenchymal localization influences their function remains unknown. We analyzed MAIT cells resident in the vascular bed of livers and showed that they represented the majority of T cells expressing NK markers and the dominant IL-17A+ T cell subset in the human liver sinusoids. In comparison with MAIT cells purified from peripheral blood, intrasinusoidal MAIT cells expressed markers of T cell activation; however, TCR-mediated cytokine production was equally suppressed in both circulating and intrasinusoidal MAIT cells. MAIT cells also expressed high levels of IL-7R, and we showed that IL-7, a cytokine produced by hepatocytes during inflammation, regulated TCR-mediated activation of MAIT cells, licensing them to dramatically increase Th1 cytokines and IL-17A production. Our quantitative and functional data indicate that MAIT cells are a specialized cell population highly adapted to exert their immune functions in the vascular network of the liver.

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Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine

Abstract: Homeostatic TH17 differentiation in the intestine is regulated by IL-1β secretion from intestinal macrophages stimulated by commensal microbiota.

Cited by 304 publications

References 24 publications

Early Inhibition of IL-1β Expression by IFN-γ Is Mediated by Impaired Binding of NF-κB to the IL-1β Promoter but Is Independent of Nitric Oxide

Early Inhibition of IL-1β Expression by IFN-γ Is Mediated by Impaired Binding of NF-κB to the IL-1β Promoter but Is Independent of Nitric Oxide

Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b ⁺ dendritic cells

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

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Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine

Abstract: Homeostatic TH17 differentiation in the intestine is regulated by IL-1β secretion from intestinal macrophages stimulated by commensal microbiota.

Cited by 304 publications

References 24 publications

Early Inhibition of IL-1β Expression by IFN-γ Is Mediated by Impaired Binding of NF-κB to the IL-1β Promoter but Is Independent of Nitric Oxide

Early Inhibition of IL-1β Expression by IFN-γ Is Mediated by Impaired Binding of NF-κB to the IL-1β Promoter but Is Independent of Nitric Oxide

Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b + dendritic cells

IL-7 Licenses Activation of Human Liver Intrasinusoidal Mucosal-Associated Invariant T Cells

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Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b ⁺ dendritic cells