Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis

Zhang, Qian; Wang, Lei; Jiang, Jintao; Lin, Shiyu; Luo, Aishu; Zhao, Pengfei; Tan, Wenfeng; Zhang, Miaojia

doi:10.3389/fimmu.2020.02040

Cited by 22 publications

(23 citation statements)

References 32 publications

(35 reference statements)

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“…HMW adiponectin induced the production of IL-6 in unstimulated but not LPS-activated human monocytes, while LMW reduced IL-6 and increased IL-10 in LPS-activated monocytes [ 55 ]. Adiponectin seems to promote the differentiation of naïve T cells into Th17 cells, contributing to synovial inflammation and bone erosions, which may be mostly dependent on AdipoR1, demonstrated in conditional AdipoR1 knockout models [ 56 ]. Other cell types such as chondrocytes, endothelial cells, and lymphocytes also showed a pro-inflammatory response to adiponectin [ 12 , 24 ], suggesting a mainly pro-inflammatory effect of adiponectin locally within the affected joints ( Figure 1 ).…”

Section: Adipokines In Autoimmune Rheumatoid Arthritismentioning

confidence: 99%

Adipokines and Autoimmunity in Inflammatory Arthritis

Neumann

Hasseli

Ohl

et al. 2021

Cells

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Adipokines are adipose tissue-derived factors not only playing an important role in metabolism but also influencing other central processes of the body, such as inflammation. In autoimmune diseases, adipokines are involved in inflammatory pathways affecting different cell types. Many rheumatic diseases belong to the group of autoimmune diseases, for example rheumatoid arthritis (RA) and psoriatic arthritis. Due to the autoimmune responses, a chronic inflammatory milieu develops, which affects the whole body, including adipose tissue. Metabolic alterations such as obesity influence inflammatory responses in autoimmune diseases. Adipokines are bioactive mediators mainly produced by adipose tissue. Due to alterations of systemic adipokine levels, their role as biomarkers with diagnostic potential has been suggested in the context of rheumatic diseases. In the affected joints of RA patients, different synoviocytes but also osteoclasts, osteoblasts, and chondrocytes produce several adipokines, contributing to the unique inflammatory microenvironment. Adipokines have been shown to be potent modulatory effectors on different cell types of the immune system but also local cells in synovial tissue, cartilage, and bone. This review highlights the most recent findings on the role of adipokines in the pathophysiology of inflammatory arthritis with a distinct focus on RA in the quickly developing research field.

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Section: Adipokines In Autoimmune Rheumatoid Arthritismentioning

confidence: 99%

Adipokines and Autoimmunity in Inflammatory Arthritis

Neumann

Hasseli

Ohl

et al. 2021

Cells

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“…However, recently Zhang et al. reported that Th17 cell differentiation is suppressed in AdipoR1-deficient mice ( 69 ), suggesting an enhancing role of AdipoR1 for the differentiation of Th17 cells. Although this apparently seems contradict with previous reports ( 11 – 13 ), this is probably because signaling through AdipoR2 is enhanced in the absence of AdipoR1.…”

Section: Discussionmentioning

confidence: 99%

The CTRP3-AdipoR2 Axis Regulates the Development of Experimental Autoimmune Encephalomyelitis by Suppressing Th17 Cell Differentiation

et al. 2021

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C1q/TNF-related proteins (CTRP) including CTRP3 are a group of secreted proteins which have a complement C1q-like domain in common, and play versatile roles in lipid metabolism, inflammation, tumor metastasis and bone metabolism. Previously, we showed that the expression of C1qtnf3, encoding CTRP3, is highly augmented in joints of autoimmune arthritis models and CTRP3-deficiency exacerbates collagen-induced arthritis in mice. However, the mechanisms how CTRP3-deficiency exacerbates arthritis still remain to be elucidated. In this study, we showed that CTRP3 was highly expressed in Th17 cell, a key player for the development of autoimmune diseases, and Th17 cell differentiation was augmented in C1qtnf3–/– mice. Th17 cell differentiation, but not Th1 cell differentiation, was suppressed by CTRP3 and this suppression was abolished by the treatment with a receptor antagonist against AdipoR2, but not AdipoR1, associated with suppression of Rorc and Stat3 expression. Furthermore, AdipoR1 and AdipoR2 agonist, AdipoRon suppressed Th17 cell differentiation via AdipoR2, but not AdipoR1. The development of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis was enhanced in C1qtnf3–/– mice associated with increase of Th17 cell population. CTRP3 inhibited MOG-induced IL-17 production from T cells by affecting both T cells and dendritic cells. These results show that CTRP3 is an endogenous regulator of Th17 differentiation, suggesting that the CTRP3-AdipoR2 axis is a good target for the treatment of Th17 cell-mediated diseases.

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“…Their unique molecular determinants are upregulated expression of Traf6 and Eomes and activation through the pathway Pu.1-Traf6-NF-κB [ 109 ]. Th17 cells are characterized by the molecular determinants mir26 [ 110 ], HIF-1, pyruvate kinase M2 (PKM2) [ 111 ] and adiponectin [ 112 ]. Treg cells (Foxp3+) have a suppressive function with respect to autoimmune reactivity [ 113 ].…”

Section: At Work For the Immune Systemmentioning

confidence: 99%

“…T cell metabolism also plays an important role in diseases like autoimmunity (e.g., systemic lupus erythematosus (SLE), graft-versus-host disease (GvHD), and rheumatoid arthritis (RA)) [ 4 ]. Th17 cells ( Table 3 ) were recently demonstrated to play an important role in RA via microRNA 26 [ 109 ], pyruvate kinase M2 (PKM2) [ 112 ], and the hormone adiponectin [ 116 ]. (5) Over-reactivity.…”

Section: At Work For the Immune Systemmentioning

confidence: 99%

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Schirrmacher¹

2020

Biomedicines

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Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria—156 brand new publications from 2019 and 2020—have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.

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Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis

Cited by 22 publications

References 32 publications

Adipokines and Autoimmunity in Inflammatory Arthritis

Adipokines and Autoimmunity in Inflammatory Arthritis

The CTRP3-AdipoR2 Axis Regulates the Development of Experimental Autoimmune Encephalomyelitis by Suppressing Th17 Cell Differentiation

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

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