High Glucose Intake Exacerbates Autoimmunity through Reactive-Oxygen-Species-Mediated TGF-β Cytokine Activation

Zhang, Dunfang; Jin, Wenwen; Wu, Rongrong; Li, Jia; Park, Sang-A; Tu, Eric; Zanvit, Peter; Xu, Junji; Liu, Ousheng; Cain, Alexander; Chen, Wanjun

doi:10.1016/j.immuni.2019.08.001

Cited by 199 publications

(177 citation statements)

References 48 publications

(57 reference statements)

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“…High sugar consumption has been suggested to be a potential environmental risk factor for the increasing incidence of several diseases including autoimmune disorders (Hu et al, 2014). Recent studies showed that high sugar intake in mice exacerbates autoimmunity in experimental models of T-cell transfer colitis and experimental autoimmune encephalomyelitis by promoting Th17 cell differentiation (Cao et al, 2017;Zhang et al, 2019). Based on our experimental findings and that of others, we postulate that the WDinduced inflammation is due to a combination of excessive fat and sugars.…”

Section: Discussionsupporting

confidence: 65%

Short-Term Exposure to a Western Diet Induces Psoriasiform Dermatitis by Promoting Accumulation of IL-17A–Producing γδ T Cells

Shi

et al. 2020

Journal of Investigative Dermatology

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A Western diet (WD)-characterized by its high fat and simple sugar content-is thought to predispose individuals to inflammatory skin diseases such as psoriasis through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity itself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to T helper type 1e/T helper type 17ebiased skin inflammation before significant body weight gain. Feeding for as little as 4 weeks with a WD promoted mild dermatitis and accumulation of IL-17Aeproducing gd T cells in the skin. Strikingly, gd T cells from WD-fed mice exhibited enriched IL-23 receptor expression and increased the potential to produce IL-17A after IL-23 stimulation. In contrast to wild-type mice, WD-fed TCRdedeficient and CCR6-deficient mice had reduced skin inflammation and IL-17A expression. Supplementation with a bile acid sequestrant, cholestyramine, prevented WD-induced skin inflammation along with a reduction in the infiltration of gd T cells and the expression of proinflammatory mediators. In summary, our data revealed dietary influences in inflammatory signaling in the skin. The dysregulation of IL-23 pathways and bile acid pathways may be key to the development of WD-associated psoriasiform dermatitis.

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Section: Discussionsupporting

confidence: 65%

Short-Term Exposure to a Western Diet Induces Psoriasiform Dermatitis by Promoting Accumulation of IL-17A–Producing γδ T Cells

Shi

et al. 2020

Journal of Investigative Dermatology

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“…Since ILA could inhibit Th17 cell polarization in a dose‐dependent manner, HSD thus exacerbated EAE by promoting Th17 cell differentiation . Not only high salt but also high glucose intake appeared to induce Th17 cells through the activation of mitochondrial ROS‐dependent TGF‐β signal and therefore enhance the severity of experimental colitis and EAE …”

Section: Th17 Cell–dependent Chronic Autoimmune Arthritismentioning

confidence: 99%

Impaired T cell receptor signaling and development of T cell–mediated autoimmune arthritis

Takeuchi

Hirota

Sakaguchi

2020

Immunological Reviews

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Mutations of the genes encoding T‐cell receptor (TCR)‐proximal signaling molecules, such as ZAP‐70, can be causative of immunological diseases ranging from T‐cell immunodeficiency to T‐cell–mediated autoimmune disease. For example, SKG mice, which carry a hypomorphic point mutation of the Zap‐70 gene, spontaneously develop T‐cell–mediated autoimmune arthritis immunopathologically similar to human rheumatoid arthritis (RA). The Zap‐70 mutation alters the sensitivity of developing T cells to thymic positive/negative selection by self‐peptides/MHC complexes, shifting self‐reactive TCR repertoire to include a dominant arthritogenic specificity and also affecting thymic development and function of autoimmune suppressive regulatory T (Treg) cells. Polyclonal self‐reactive T cells, including potentially arthritogenic T cells, thus produced by the thymus recognize self‐peptide/MHC complexes on antigen‐presenting cells (APCs) in the periphery and stimulate them to produce cytokines including IL‐6 to drive the arthritogenic T cells to differentiate into arthritogenic T‐helper 17 (Th17) cells. Insufficient Treg suppression or activation of APCs via microbial and other environmental stimuli evokes arthritis by activating granulocyte‐macrophage colony‐stimulating factor‐secreting effector Th17 cells, mediating chronic bone‐destructive joint inflammation by activating myeloid cells, innate lymphoid cells, and synoviocytes in the joint. These findings obtained from the study of SKG mouse arthritis are instrumental in understanding how arthritogenic T cells are produced, become activated, and differentiate into effector T cells mediating arthritis, and may help devising therapeutic measures targeting autoimmune pathogenic Th17 cells or autoimmune‐suppressing Treg cells to treat and prevent RA.

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“…ROS increases active extracellular TGF-β levels. This cytokine influences RORγt, thus activating transcription of IL-17 and leading to differentiation of TH17 cells (98).…”

Section: Figure 1 | (A)mentioning

confidence: 99%

Role of Non-coding RNAs in the Pathogenesis of Endometriosis

2020

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Endometriosis is a disorder characterized by the presence of endometrial glands and stroma like lesions outside of the uterus. Although several hypothesis have tried to explain the underlying cause of endometriosis, yet the main cause remained obscure. Recent studies have shown contribution of non-coding RNAs in the pathogenesis of endometriosis. Two classes of these transcripts namely long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have mostly attracted attention of researchers. Several studies have reported aberrant expression of these transcripts in affected tissues from patients as well as animal models. Modulation of important signaling pathways such as PI3K/AKT, P38-MAPK, ERK1/2-MAPK and Wnt-β catenin by miRNAs and lncRNAs have potentiated these molecules as biomarkers or therapeutic agents in endometriosis. Single nucleotide polymorphisms with miR-126, miR-143 and miR-146b have been associated with risk of endometriosis. Moreover, miRNAs and lncRNAs control inflammatory responses, cell proliferation, angiogenesis and tissue remodeling, thus understanding the role of these transcripts in endometriosis is a possible way to develop novel diagnostic tests and therapeutic targets for this disorder.

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High Glucose Intake Exacerbates Autoimmunity through Reactive-Oxygen-Species-Mediated TGF-β Cytokine Activation

Cited by 199 publications

References 48 publications

Short-Term Exposure to a Western Diet Induces Psoriasiform Dermatitis by Promoting Accumulation of IL-17A–Producing γδ T Cells

Short-Term Exposure to a Western Diet Induces Psoriasiform Dermatitis by Promoting Accumulation of IL-17A–Producing γδ T Cells

Impaired T cell receptor signaling and development of T cell–mediated autoimmune arthritis

Role of Non-coding RNAs in the Pathogenesis of Endometriosis

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