From the diet to the nucleus: Vitamin A and TGF-β join efforts at the mucosal interface of the intestine

Mucida, Daniel; Park, Yunji; Cheroutre, Hilde

doi:10.1016/j.smim.2008.08.001

Cited by 83 publications

(64 citation statements)

References 86 publications

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“…Additionally, it has recently been reported that bacterialinduced metabolites support the differentiation of T cells, including Th17 cells (40). To demonstrate whether P. UF1-induced metabolites can prime Th17 cell differentiation, metabolomic analyses of P. UF1-gavaged H2-Ab1 -/-mice compared with H2-Ab1 -/-mice plus CD4 + T cells and PBS-gavaged H2-Ab1 -/-mice were performed.…”

Section: Characterization Of P Uf1 Bacteriummentioning

confidence: 99%

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

Colliou¹,

Ge²,

Sahay³

et al. 2017

Journal of Clinical Investigation

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Section: Characterization Of P Uf1 Bacteriummentioning

confidence: 99%

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

Colliou¹,

Ge²,

Sahay³

et al. 2017

Journal of Clinical Investigation

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“…In humans, vitamin A is absorbed from the diet. Its principal physiologically significant metabolite in vivo is the trans isomer of retinoic acid, all-trans retinoic acid (ATRA) (92). Recent studies have shown that ATRA markedly influences the fate of naïve T cells activated in the presence of TGF␤1.…”

Section: Immune Deviation In the It Reg /Th17 Pathway: A Novelmentioning

confidence: 99%

The Treg/Th17 Cell Balance: A New Paradigm for Autoimmunity

2009

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Regulatory T cells and T helper 17 cells are two recently described lymphocyte subsets with opposing actions. In this review, we discuss the mechanisms that promote development of these cells from common precursors and the specific factors that impact their cell numbers and function. Altered regulation of this key developmental checkpoint may contribute to the pathophysiology of autoimmune diseases by tipping the balance toward inflammation. We also present recent findings that suggest how the equilibrium between regulatory T cells and proinflammatory T helper subsets might be pharmacologically restored for therapeutic benefit. (Pediatr Res 65: 26R-31R, 2009) T he recent discovery of two novel subsets of CD4 ϩ T lymphocytes has led to a paradigm shift in the understanding of how autoimmune responses are both mediated and regulated. One of these cell subsets, CD4 ϩ T helper 17 (Th17) lymphocytes, is a key effector cell in rodent models of human diseases including collagen arthritis and experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. A second CD4 ϩ T lymphocyte subset, termed regulatory T (T reg ) cells, is essential for dominant immunologic tolerance. Surprisingly, both Th17 and T reg cells can develop from naïve CD4 ϩ T cell precursors under the influence of the same cytokine, transforming growth factor ␤1 (TGF␤1). In this review, we discuss the ontogeny of T reg and Th17 cells, as well as their known immune functions. We present the hypothesis that certain forms of autoimmunity may result when CD4 ϩ T cell differentiation is biased away from T reg cells and toward the Th17 cell phenotype. Finally, we discuss ways that the Th17/T reg cell balance might be modified to restore immune homeostasis, resulting in therapeutic benefit in autoimmune conditions. Regulatory T Lymphocytes CD4ϩ lymphocytes with suppressor properties have been known to exist for many years. However, the central role of CD4 ϩ CD25 ϩ T reg cells expressing the transcription factor forkhead box protein 3 (Foxp3) in immune regulation was initially disclosed by studies involving the inbred Scurfy mouse strain. In these animals, frameshift mutations in Foxp3 transmitted by X-linked inheritance result in a fatal syndrome of extensive immune activation, leading to oversecretion of numerous cytokines and multiorgan infiltration by inflammatory cells (1). Orthologous mutations were shown to be responsible for the human condition immune dysregulationpolyendocrinopathy-enteropathy-X-linked (2-4). Foxp3 gene transfer to CD4 ϩ CD25 Ϫ T cells confers suppressive properties (5-7), confirming that Foxp3 in these cells is sufficient to suppress proliferation and cytokine secretion by effector Th cells. Although Foxp3 itself may not specify T reg cell lineage commitment (8,9), maintenance of the regulatory phenotype in thymically derived T reg cells requires constitutive Foxp3 expression (10). Moreover, depletion of T reg cells in adult or neonatal mice induces the Scurfy phenotype, whereas adoptive transfer of relative...

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“…Recently, it has been demonstrated that the presence of RA enhances TGF-β signaling by increasing the expression and phosphorylation of Smad3. This results in increased Foxp3 expression, even in the presence of Th17-inducing cytokines such as IL-6 or IL-21 [40][41][42].…”

Section: Introductionmentioning

confidence: 99%

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

et al. 2014

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CD4 + CD25 + Foxp3 + regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-β. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-β, RA, and IL-2 resulted in a striking enrichment of Foxp3 + T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive capacity. Finally, RA-iTreg cells showed alloantigen-specific immunosuppressive capacity in a skin allograft model in immunodeficient mice. Altogether, these data indicate that functional and stable allogeneic-specific Treg cells may be generated using TGF-β, RA, and IL-2. Thus, RA-iTreg cells may have a potential use in the development of more effective cellular therapies in clinical transplantation. Keywords: Allogeneic regulatory T cells r Homing r Retinoic acid r Tolerance r TransplantationAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionRegulatory T (Treg) cells are responsible for inducing and maintaining peripheral tolerance [1]. Treg cells are classified into two Correspondence: Dr. Daniela Sauma e-mail: dsauma@u.uchile.cl major subpopulations: thymus-derived Treg cells, which are generated in the thymus and circulate in the periphery as functional mature Treg cells [2][3][4], and peripherally derived Treg cells, which are generated in the periphery from CD4 + CD25 − naive * These authors contributed equally to this work.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 452-463 Immunomodulation 453T cells [5][6][7]. Treg cells target effector T cells and dendritic cells (DCs) by modulating their maturation and function through several mechanisms that suppress immune responses [8][9][10]; these include secretion of inhibitory cytokines (IL-10, IL-35, and TGF-β), granzyme/perforin-dependent mediated cytolysis, metabolic disruption [11][12][13][14][15], and the expression of LAG3 and CTLA4, which alter DC function [16,17]. In addition to the aforementioned mechanisms, Treg-cell suppressive capacity is dependent on Treg-cell migration and retention in the microenvironment where regulation is required. Differential expression patterns of chemokine receptors (such as CCR4, CCR5, and CCR9), integrins (α4β7), and selectins (CD62L) contribute to selective retention and trafficking of Treg cells and allow their appropriate localization during ...

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From the diet to the nucleus: Vitamin A and TGF-β join efforts at the mucosal interface of the intestine

Cited by 83 publications

References 86 publications

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation

The Treg/Th17 Cell Balance: A New Paradigm for Autoimmunity

Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

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