PPARs at the crossroads of T cell differentiation and type 1 diabetes

作者全名："Riaz, Farooq; Wei, Ping; Pan, Fan"

作者地址："[Riaz, Farooq; Pan, Fan] Chinese Acad Sci, Shenzhen Inst Adv Technol SIAT, Shenzhen, Peoples R China; [Wei, Ping] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders Chongqing, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China"

通信作者："Pan, F (通讯作者)，Chinese Acad Sci, Shenzhen Inst Adv Technol SIAT, Shenzhen, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001092291400001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Review

关键词：type-1 diabetes; peroxisome proliferator-activated receptors; autoimmunity; CD4+T cells; Th17; regulatory T cells

摘要："T-cell-mediated autoimmune type 1 diabetes (T1D) is characterized by the immune-mediated destruction of pancreatic beta cells (beta-cells). The increasing prevalence of T1D poses significant challenges to the healthcare system, particularly in countries with struggling economies. This review paper highlights the multifaceted roles of Peroxisome Proliferator-Activated Receptors (PPARs) in the context of T1D, shedding light on their potential as regulators of immune responses and beta-cell biology. Recent research has elucidated the intricate interplay between CD4+ T cell subsets, such as Tregs and Th17, in developing autoimmune diseases like T1D. Th17 cells drive inflammation, while Tregs exert immunosuppressive functions, highlighting the delicate balance crucial for immune homeostasis. Immunotherapy has shown promise in reinstating self-tolerance and restricting the destruction of autoimmune responses, but further investigations are required to refine these therapeutic strategies. Intriguingly, PPARs, initially recognized for their role in lipid metabolism, have emerged as potent modulators of inflammation in autoimmune diseases, particularly in T1D. Although evidence suggests that PPARs affect the beta-cell function, their influence on T-cell responses and their potential impact on T1D remains largely unexplored. It was noted that PPAR alpha is involved in restricting the transcription of IL17A and enhancing the expression of Foxp3 by minimizing its proteasomal degradation. Thus, antagonizing PPARs may exert beneficial effects in regulating the differentiation of CD4+ T cells and preventing T1D. Therefore, this review advocates for comprehensive investigations to delineate the precise roles of PPARs in T1D pathogenesis, offering innovative therapeutic avenues that target both the immune system and pancreatic function. This review paper seeks to bridge the knowledge gap between PPARs, immune responses, and T1D, providing insights that may revolutionize the treatment landscape for this autoimmune disorder. Moreover, further studies involving PPAR agonists in non-obese diabetic (NOD) mice hold promise for developing novel T1D therapies."

基金机构："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. FP's work was supported by the National Key Ramp;D Program of China (2021YFC2400500) and (2022YFC2403000), the National Natural Science [2021YFC2400500, 2022YFC2403000]; National Key Ramp;D Program of China [32170925]; National Natural Science Foundation of China [JCYJ2022081800807016]; Shenzhen Science and Technology Program; CAS [CSTB2022NSCQ-MSX1069]; Natural Science Foundation of Chongqing Grant [CX2022118]; Chongqing for overseas Scholars"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. FP's work was supported by the National Key R & D Program of China (2021YFC2400500) and (2022YFC2403000), the National Natural Science Foundation of China (Grant 32170925), Shenzhen Science and Technology Program (KQTD20210811090115019), the Shenzhen Science and Technology Program (JCYJ2022081800807016), the startup fund of SIAT and CAS. PW's work was supported by the Natural Science Foundation of Chongqing Grant CSTB2022NSCQ-MSX1069, the Chongqing for overseas Scholars Grant CX2022118."