A Central Role for Atg5 in Microbiota-Dependent Foxp3+ RORγt+ Treg Cell Preservation to Maintain Intestinal Immune Homeostasis

Plaza-Sirvent, Carlos; Zhao, Bei; Bronietzki, Alisha W.; Pils, Marina C.; Tafrishi, Neda; Schuster, Marc; Strowig, Till; Schmitz, Ingo

doi:10.3389/fimmu.2021.705436

Cited by 5 publications

(7 citation statements)

References 58 publications

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“…Kabat et al reported that Atg16l1-deficient CD4 + T cells show a reduced population of Treg cells ( Kabat et al, 2016 ). Aged Atg16l1 f/f CD4-Cre mice and aged Atg5 f/f Foxp3-Cre mice showed increased inflammation in the colon and greater weight loss compared with normal control mice ( Kabat et al, 2016 ; Plaza-Sirvent et al, 2021 ).…”

Section: Chronic Inflammatory Diseasesmentioning

confidence: 91%

The Role of Autophagy in the Function of CD4+ T Cells and the Development of Chronic Inflammatory Diseases

2022

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Uncontrolled acute inflammation progresses to persistent inflammation that leads to various chronic inflammatory diseases, including asthma, Crohn’s disease, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. CD4+ T cells are key immune cells that determine the development of these chronic inflammatory diseases. CD4+ T cells orchestrate adaptive immune responses by producing cytokines and effector molecules. These functional roles of T cells vary depending on the surrounding inflammatory or anatomical environment. Autophagy is an important process that can regulate the function of CD4+ T cells. By lysosomal degradation of cytoplasmic materials, autophagy mediates CD4+ T cell-mediated immune responses, including cytokine production, proliferation, and differentiation. Furthermore, through canonical processes involving autophagy machinery, autophagy also contributes to the development of chronic inflammatory diseases. Therefore, a targeted intervention of autophagy processes could be used to treat chronic inflammatory diseases. This review focuses on the role of autophagy via CD4+ T cells in the pathogenesis and treatment of such diseases. In particular, we explore the underlying mechanisms of autophagy in the regulation of CD4+ T cell metabolism, survival, development, proliferation, differentiation, and aging. Furthermore, we suggest that autophagy-mediated modulation of CD4+ T cells is a promising therapeutic target for treating chronic inflammatory diseases.

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Section: Chronic Inflammatory Diseasesmentioning

confidence: 91%

The Role of Autophagy in the Function of CD4+ T Cells and the Development of Chronic Inflammatory Diseases

2022

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“…The transplantation of healthy human feces can ameliorate DSS-induced UC in GF mice and increase the number of IL-17-producing Tregs, illustrating that gut probiotics can enhance UC by promoting IL-17-producing Treg differentiation [136]. Moreover, mice lacking Arkadia or Atg5-mediated differentiation of IL-17-producing Tregs display intestinal inflammation [13,61]. It has also been reported that in the context of inflammatory bowel disease, ILC3s can alleviate intestinal inflammation by promoting IL-17-producing Treg differentiation [168].…”

Section: The Amelioration Of Ibd By Promoting Il-17-producing Treg Di...mentioning

confidence: 99%

“…IL-17-producing Tregs have been identified not only in peripheral blood and lymphoid tissue but also in various organs, including the intestine [ 13 ], spleen [ 14 ], lymph nodes [ 14 ], lung [ 15 ], liver [ 15 ], kidney [ 16 ], and other tissues. In contrast to conventional Tregs, IL-17-producing Tregs exhibit distinct phenotypic characteristics, characterized by high levels of RORγT, inducible co-stimulator (ICOS), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and CD103 expression.…”

Section: Introductionmentioning

confidence: 99%

“…In Treg specific Atg5-deficient mice ( Foxp3 cre Atg5 fl/fl ), the expression of IL-17-producing Tregs in the gut is nearly undetectable. However, further investigations are required to elucidate how Atg5 regulates IL-17-producing Treg differentiation and the role of glycolysis in this process [ 13 ]. Techniques such as metabolomics may provide valuable insights into the metabolic regulatory mechanisms governing IL-17-producing Treg differentiation.…”

Section: Introductionmentioning

confidence: 99%

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The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology

Cui,

Wang,

et al. 2024

Cell Commun Signal

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The changes in T regulatory cell (Treg) and T helper cell (Th) 17 ratios holds paramount importance in ensuring internal homeostasis and disease progression. Recently, novel subsets of Treg and Th17, namely IL-17-producing Treg and IL-10-producing Th17 have been identified. IL-17-producing Treg and IL-10-producing Th17 are widely considered as the intermediates during Treg/Th17 transformation. These “bi-functional” cells exhibit plasticity and have been demonstrated with important roles in multiple physiological functions and disease processes. Yin and Yang represent opposing aspects of phenomena according to the ancient Chinese philosophy “Yin-Yang” theory. Furthermore, Yin can transform into Yang, and vice versa, under specific conditions. This theory has been widely used to describe the contrasting functions of immune cells and molecules. Therefore, immune-activating populations (Th17, M1 macrophage, etc.) and immune overreaction (inflammation, autoimmunity) can be considered Yang, while immunosuppressive populations (Treg, M2 macrophage, etc.) and immunosuppression (tumor, immunodeficiency) can be considered Yin. However, another important connotation of “Yin-Yang” theory, the conversion between Yin and Yang, has been rarely documented in immune studies. The discovery of IL-17-producing Treg and IL-10-producing Th17 enriches the meaning of “Yin-Yang” theory and further promotes the relationship between ancient “Yin-Yang” theory and modern immunology. Besides, illustrating the functions of IL-17-producing Treg and IL-10-producing Th17 and mechanisms governing their differentiation provides valuable insights into the mechanisms underlying the dynamically changing statement of immune statement in health and diseases.

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“…Along these lines, RORγt + Tregs may be important factors in limiting microbial dysbiosis and intestinal inflammation [75], and the production of RORγt + Tregs depends on the presence of gut microbes, including Clostridium, and other members of Firmicutes, Bacteroidetes, and Proteobacteria support their differentiation [53,58].…”

Section: Scfas Enhanced the Expression Of Rorγt + Treg Cellsmentioning

confidence: 99%

Gut Microbiota Promotes Immune Tolerance by Regulating RORγt+ Treg Cells in Food Allergy

Ning

Lei

Rui

et al. 2022

Advanced Gut & Microbiome Research

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Food allergy is a significant public health problem troubling people, and the incidence has been on the rise in the past decade. Emerging evidence suggests an influence of the gut microbiota in susceptibility to food allergies. Epidemiological studies have shown an association between altered exposure to the microbiome and the risk of food allergies. Intervention of the gut microbiota in germ-free mice or supplementation of probiotics can regulate the proliferation of regulatory T (Treg) cells in mice and inhibit food allergy by promoting the expression of receptor-associated orphan γt+ (RORγt+) regulatory T (Treg) cells and inhibiting the proliferation of T helper 2 (Th2) and Th17 cells. This paper reviews the current research progress on how the gut microbiota enhances immune tolerance to prevent food allergy through RORγt+ Treg, hoping to provide some new ideas and effective targets for the prophylaxis of food allergy.

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A Central Role for Atg5 in Microbiota-Dependent Foxp3+ RORγt+ Treg Cell Preservation to Maintain Intestinal Immune Homeostasis

Cited by 5 publications

References 58 publications

The Role of Autophagy in the Function of CD4+ T Cells and the Development of Chronic Inflammatory Diseases

The Role of Autophagy in the Function of CD4+ T Cells and the Development of Chronic Inflammatory Diseases

The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology

Gut Microbiota Promotes Immune Tolerance by Regulating RORγt+ Treg Cells in Food Allergy

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