Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation

Mielke, Lisa A.; Jones, Sarah A.; Raverdeau, Mathilde; Higgs, Rowan; Stefańska, Anna; Groom, Joanna R; Misiak, Alicja; Dungan, Lara S.; Sutton, Caroline E.; Streubel, Gundula; Bracken, Adrian P.; Mills, Kingston H. G.

doi:10.1084/jem.20121588

Cited by 264 publications

(261 citation statements)

References 29 publications

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“…Consistent with the effect of CD4 + T cells, we found that RA inhibits IL-17A production by gd T cells but, interestingly, enhances the production of IL-22 by gd T cells and group 3 ILCs stimulated with IL-1b and IL-23 (80). Furthermore, in vivo administration of RA promotes recovery from intestinal inflammation induced by dextran sulfate sodium or following infection with Citrobacter rodentium, and this is associated with enhanced production of IL-22 and the antimicrobial peptides REG3b and REG3g (80). Consistent with the protective effects of atRA, Chenery et al (81) showed that mice lacking the RA-degrading enzyme CYP26B1 are protected against T cell-induced intestinal inflammation.…”

Section: Impact Of Ra On Gd T Cells Nk Cells and Innate Lymphoid Cellssupporting

confidence: 85%

Modulation of T Cell and Innate Immune Responses by Retinoic Acid

Raverdeau

Mills

2014

The Journal of Immunology

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186

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Retinoic acid (RA) is produced by a number of cell types, including macrophages and dendritic cells, which express retinal dehydrogenases that convert vitamin A to its main biologically active metabolite, all-trans RA. All-trans RA binds to its nuclear retinoic acid receptors that are expressed in lymphoid cells and act as transcription factors to regulate cell homing and differentiation. RA production by CD103+ dendritic cells and alveolar macrophages functions with TGF-β to promote conversion of naive T cells into Foxp3+ regulatory T cells and, thereby, maintain mucosal tolerance. Furthermore, RA inhibits the differentiation of naive T cells into Th17 cells. However, Th1 and Th17 responses are constrained during vitamin A deficiency and in nuclear RA receptor α–defective mice. Furthermore, RA promotes effector T cell responses during infection or autoimmune diseases. Thus, RA plays a role in immune homeostasis in the steady-state but activates pathogenic T cells in conditions of inflammation.

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Section: Impact Of Ra On Gd T Cells Nk Cells and Innate Lymphoid Cellssupporting

confidence: 85%

Modulation of T Cell and Innate Immune Responses by Retinoic Acid

Raverdeau

Mills

2014

The Journal of Immunology

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186

161

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“…We have shown that the size of these lymphoid organs determined the efficiency by which a viral infection could be cleared at adult age (16). An essential role for vitamin A in adult mice during Citrobacter rodentium infection and dextran sodium sulfate-induced colitis has been shown (14,15), indicating an important role for IL-22 production during intestinal inflammation. However, these studies did not consider the reduced number of SILTs in the absence of dietary intake of vitamin A, which will also have its effect on the efficiency of the immune response.…”

Section: Temporary Postnatal Inhibition Of Ra Signaling Affects Silt mentioning

confidence: 94%

“…For instance, it has been shown that dietary AhR ligands are able to control the function and maintenance of group 3 ILCs postnatally, which consequently has an impact on the formation of CPs and isolated lymphoid follicles (11)(12)(13). Additionally, it was first shown by Mielke et al (14) that not only intestinal gd T cells but also IL-22-producing ILCs are controlled by the active metabolite of vitamin A, retinoic acid (RA). The importance of vitamin A for ILCs was even further established, as in the absence of vitamin A RORg + ILC3s are reduced, whereas group 2 ILCs are enhanced (15).…”

mentioning

confidence: 99%

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Goverse

Labão-Almeida²,

Ferreira³

et al. 2016

The Journal of Immunology

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Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR− and NCR+ ILC3 subsets in the small intestine of mice raised on a vitamin A–deficient diet. Additionally, the percentages of IL-22–producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR− ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A–deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid–related orphan receptor γt–Cre × RARα-DN mice had reduced numbers of NCR− and NCR+ ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid–related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines.

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“…The requirement for Clostridia-induced IL-22 production for the expansion of colonic Foxp3 + Tregs was examined by i.p. injection of 500 μg of clone IL-22JOP (eBioscience), as previously described (39).…”

mentioning

confidence: 99%

Commensal bacteria protect against food allergen sensitization

Stefka

Feehley

Tripathi

et al. 2014

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

663

646

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Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.microbiome | barrier | IL-22

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Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation

Abstract: Retinoic acid attenuates colitis and is associated with increased IL-22 production from γδ T cells and innate lymphoid cells and enhanced antimicrobial peptide expression.

Cited by 264 publications

References 29 publications

Modulation of T Cell and Innate Immune Responses by Retinoic Acid

Modulation of T Cell and Innate Immune Responses by Retinoic Acid

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Commensal bacteria protect against food allergen sensitization

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