Dataset Information

TGF-? limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.

ABSTRACT: M?s promote tissue injury or repair depending on their activation status and the local cytokine milieu. It remains unclear whether the immunosuppressive effects of transforming growth factor ? (TGF-?) serve a nonredundant role in M? function in vivo. We generated M?-specific transgenic mice that express a truncated TGF-? receptor II under control of the CD68 promoter (CD68TGF-?DNRII) and subjected these mice to the dextran sodium sulfate (DSS) model of colitis. CD68TGF-?DNRII mice have an impaired ability to resolve colitic inflammation as demonstrated by increased lethality, granulocytic inflammation, and delayed goblet cell regeneration compared with transgene negative littermates. CD68TGF-?DNRII mice produce significantly less IL-10, but have increased levels of IgE and numbers of IL-33+ M?s than controls. These data are consistent with associations between ulcerative colitis and increased IL-33 production in humans and suggest that TGF-? may promote the suppression of intestinal inflammation, at least in part, through direct effects on M? function.

SUBMITTER: Rani R

PROVIDER: S-EPMC3139176 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TGF-β limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.

Rani Reena R Smulian Alan G AG Greaves David R DR Hogan Simon P SP Herbert De'Broski R DR

European journal of immunology 20110527 7

Mϕs promote tissue injury or repair depending on their activation status and the local cytokine milieu. It remains unclear whether the immunosuppressive effects of transforming growth factor β (TGF-β) serve a nonredundant role in Mϕ function in vivo. We generated Mϕ-specific transgenic mice that express a truncated TGF-β receptor II under control of the CD68 promoter (CD68TGF-βDNRII) and subjected these mice to the dextran sodium sulfate (DSS) model of colitis. CD68TGF-βDNRII mice have an impair ...[more]

PMID: 21469118

Similar Datasets

Project description:IntroductionToll-like receptor (TLR)4 promotes joint inflammation in mice. Despite that several studies report a functional link between TLR4 and interleukin-(IL-)1? in arthritis, TLR4-mediated regulation of the complicated cytokine network in arthritis is poorly understood. To address this, we investigated the mechanisms by which TLR4 regulates the cytokine network in antibody-induced arthritis.MethodsTo induce arthritis, we injected mice with K/BxN serum. TLR4-mediated pathogenesis in antibody-induced arthritis was explored by measuring joint inflammation, cytokine levels and histological alteration.ResultsCompared to wild type (WT) mice, TLR4-/- mice showed attenuated arthritis and low interferon (IFN)-?, IL-12p35 and IL-1? transcript levels in the joints, but high transforming growth factor (TGF)-? expression. Injection of lipopolysaccharide (LPS) enhanced arthritis and exaggerated joint cytokine alterations in WT, but not TLR4-/- or IL-12p35-/- mice. Moreover, STAT4 phosphorylation in joint cells and intracellular IL-12p35 expression in macrophages, mast cells and Gr-1+ cells were detected in WT mice with arthritis and enhanced by LPS injection. Therefore, IL-12p35 appears to act downstream of TLR4 in antibody-induced arthritis. TLR4-mediated IL-12 production enhanced IFN-? and IL-1? production via T-bet and pro-IL-1? production. Recombinant IL-12, IFN-? and IL-1? administration restored arthritis, but reduced joint TGF-? levels in TLR4-/- mice. Moreover, a TGF-? blockade restored arthritis in TLR4-/- mice. Adoptive transfer of TLR4-deficient macrophages and mast cells minimally altered joint inflammation and cytokine levels in macrophage- and mast cell-depleted WT mice, respectively, whereas transfer of WT macrophages or mast cells restored joint inflammation and cytokine expression. Gr-1+ cell-depleted splenocytes partially restored arthritis in TLR4-/- mice.ConclusionTLR4-mediated IL-12 production by joint macrophages, mast cells and Gr-1+ cells enhances IFN-? and IL-1? production, which suppresses TGF-? production, thereby promoting antibody-induced arthritis.

Dataset Information

TGF-? limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.

Publications

TGF-β limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets