Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in TH17 cells

Rutz, Sascha; Noubade, Rajkumar; Eidenschenk, Céline; Ota, Naruhisa; Zeng, Wenwen; Zheng, Yan; Hackney, Jason A.; Ding, Jiabing; Singh, Harinder; Ouyang, Wenjun

doi:10.1038/ni.2134

Cited by 182 publications

(206 citation statements)

References 50 publications

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“…Therefore, B7h triggering in DCs may promote expansion of differentiated Th17 cells through the increased IL-23 secretion, which was supported by the finding that mDCs ICOS stimulated higher secretion of IL-17A and IL-17F than did plain mDCs in MLC assays. By contrast, they did not influence secretion of IL-21 and IL-22, secreted by subsets of Th17 cells (49,50). Therefore, B7h triggering seemed to modulate DCs maturation by increasing their ability to expand Th17 cells, which was intriguing in light of data showing that the triggering of ICOS on T cells supports differentiation of Th17 cells in the presence of appropriate cytokine milieus (32).…”

Section: Discussionmentioning

confidence: 83%

Triggering of B7h by the ICOS Modulates Maturation and Migration of Monocyte-Derived Dendritic Cells

Occhipinti

Dianzani

Chiocchetti

et al. 2013

The Journal of Immunology

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B7h, expressed by several cell types, binds ICOS expressed by activated T cells. We have previously shown that B7h triggering by ICOS-Fc inhibits human endothelial cell adhesiveness. This work investigated the effect of ICOS-Fc on human monocyte-derived dendritic cells (DCs). We found that DCs matured with LPS in the presence of ICOS-Fc (mDCsICOS) produced greater amounts of IL-23 and IL-10, and promoted a higher secretion of IL-17A and IL-17F in MLCs than did those DCs matured with LPS alone (mDCs). Moreover, mDCsICOS pulsed with the keyhole limpet hemocyanin Ag during the maturation phase were better stimulators of Ag-specific MHC class I–, but not class II–restricted T cells than mDCs. This was probably due to promotion of cross-presentation because it was not detected when the Flu-MA58–66 Ag was directly loaded on already matured DCs and mDCsICOS. Finally, ICOS-Fc inhibited the adhesion of both immature DCs and mDCs to vascular and lymphoid endothelial cells, their migratory activity, and the expression of the Rac-1 activator β-Pix involved in cell motility. These data suggest that B7h stimulation modulates DC function with effects on their maturation and recruitment into tissues. This opens a novel view on the use of interactors of the ICOS:B7h system as immunomodulatory drugs.

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Section: Discussionmentioning

confidence: 83%

Triggering of B7h by the ICOS Modulates Maturation and Migration of Monocyte-Derived Dendritic Cells

Occhipinti

Dianzani

Chiocchetti

et al. 2013

The Journal of Immunology

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“…In contrast, during experimental autoimmune encephalomyelitis, TGF-β1 promotes the generation of Th17 cells in the presence of IL-6, which leads to disease development in an autocrine manner (14), indicating that T cell-produced TGF-β1 differentially regulates Th1 and Th17 cell-mediated autoimmune diseases. However, the regulation of CD4 + T-cell differentiation by TGF-β1 is context dependent, as TGF-β1 has been shown to suppress IL-22 and GM-CSF production from Th17 cells (16,17), whereas it promotes Th9 cell differentiation in the presence of IL-4 (18,19). Thus, the contribution of T cellproduced TGF-β1 in diabetogenic CD4 + T-cell differentiation and spontaneous T1D development is still unknown.…”

Section: Tgf-β Signaling In T Cells Is Critical For Peripheral T-cellmentioning

confidence: 98%

Excessive Th1 responses due to the absence of TGF-β signaling cause autoimmune diabetes and dysregulated Treg cell homeostasis

Ishigame

Zenewicz

Sanjabi

et al. 2013

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

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TGF-β signaling in T cells is critical for peripheral T-cell tolerance by regulating effector CD4 + T helper (Th) cell differentiation. However, it is still controversial to what extent TGF-β signaling in Foxp3 + regulatory T (Treg) cells contributes to immune homeostasis. Here we showed that abrogation of TGF-β signaling in thymic T cells led to rapid type 1 diabetes (T1D) development in NOD mice transgenic for the BDC2.5 T-cell receptor. Disease development in these mice was associated with increased peripheral Th1 cells, whereas Th17 cells and Foxp3 + Treg cells were reduced. Blocking of IFN-γ signaling alone completely suppressed diabetes development in these mice, indicating a critical role of Th1 cells in this model. Furthermore, deletion of TGF-β signaling in peripheral effector CD4 + T cells, but not Treg cells, also resulted in rapid T1D development, suggesting that conventional CD4 + T cells are the main targets of TGF-β to suppress T1D. TGF-β signaling was dispensable for Treg cell function, development, and maintenance, but excessive IFN-γ production due to the absence of TGF-β signaling in naive CD4 + T cells indirectly caused dysregulated Treg cell homeostasis. We further showed that T cell–derived TGF-β1 was critical for suppression of Th1 cell differentiation and T1D development. These results indicate that autocrine/paracrine TGF-β signaling in diabetogenic CD4 + T cells, but not Treg cells, is essential for controlling T1D development.

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“…In Th17 cells, TGF-b also differentially regulates IL-22 and IL-17 expression. In the absence of TGF-b, IL-6 induces IL-22 (Basu et al 2012); however, in the presence of TGF-b, expression of cMaf, a repressor of Il22 gene expression, is induced (Rutz et al 2011). Such opposing effects of TGF-b on Th17-associated cytokines may contribute to the regulatory or pathogenic functions of these cells.…”

Section: Peripheral Homeostasismentioning

confidence: 99%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

477

306

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Transforming growth factor b (TGF-b) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-b alters immunity under various conditions. Under steady-state conditions, TGF-b regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-b inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral ( p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-b controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-b plays a pivotal role in maintaining peripheral tolerance against self-and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.

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Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in TH17 cells

Cited by 182 publications

References 50 publications

Triggering of B7h by the ICOS Modulates Maturation and Migration of Monocyte-Derived Dendritic Cells

Triggering of B7h by the ICOS Modulates Maturation and Migration of Monocyte-Derived Dendritic Cells

Excessive Th1 responses due to the absence of TGF-β signaling cause autoimmune diabetes and dysregulated Treg cell homeostasis

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

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