Energy status regulates levels of the RAR/RXR ligand 9-cis-retinoic acid in mammalian tissues: Glucose reduces its synthesis in β-cells

Yoo, Hong Sik; Moss, Kristin Obrochta; Cockrum, Michael A.; Woo, Wonsik; Napoli, Joseph L.

doi:10.1016/j.jbc.2023.105255

Cited by 4 publications

(1 citation statement)

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“…After ligand binding, homo- or heterodimers of the receptors recruit coactivators and initiate gene transcription by binding to retinoic acid response elements located within the promoters of target genes [ 20 ]. 9-cis-retinoic acid (9cRA), endogenous bioactive metabolite formed by spontaneous isomerization of all-trans RA, binds with high affinity to both RARs and RXRs in vitro [ 21 ]. It was found, that rodent Sertoli cells express both RARα and RXRβ [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

9-cis-retinoic acid signaling in Sertoli cells regulates their immunomodulatory function to control lymphocyte physiology and Treg differentiation

Kamińska,

Pardyak,

Lustofin

et al. 2024

Reprod Biol Endocrinol

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Background Testis is an immune privileged organ, which prevents the immune response against sperm antigens and inflammation. Testicular cells responsible for immune tolerance are mainly Sertoli cells, which form the blood-testis barrier and produce immunosuppressive factors. Sertoli cells prevent inflammation in the testis and maintain immune tolerance by inhibiting proliferation and inducing lymphocyte apoptosis. It has been shown that 9-cis-retinoic acid (9cRA) blocks ex vivo apoptosis of peripheral blood lymphocytes and promotes the differentiation of Treg cells in the gut. However, the role of retinoid signaling in regulating the immune privilege of the testes remains unknown. Objective The aim of this study was to determine whether 9cRA, acting via the retinoic acid receptors (RAR) and the retinoic X receptors (RXR), controls the immunomodulatory functions of Sertoli cells by influencing the secretion of anti-inflammatory/pro-inflammatory factors, lymphocyte physiology and Treg cell differentiation. Methods Experiments were performed using in vitro model of co-cultures of murine Sertoli cells and T lymphocytes. Agonists and antagonists of retinoic acid receptors were used to inhibit/stimulate retinoid signaling in Sertoli cells. Results Our results have demonstrated that 9cRA inhibits the expression of immunosuppressive genes and enhances the expression of pro-inflammatory factors in Sertoli cells and lymphocytes, increases lymphocyte viability and decreases apoptosis rate. Moreover, we have found that 9cRA blocks lymphocyte apoptosis acting through both RAR and RXR and inhibiting FasL/Fas/Caspase 8 and Bax/Bcl-2/Caspase 9 pathways. Finally, we have shown that 9cRA signaling in Sertoli cells inhibits Treg differentiation. Conclusion Collectively, our results indicate that retinoid signaling negatively regulates immunologically privileged functions of Sertoli cells, crucial for ensuring male fertility. 9cRA inhibits lymphocyte apoptosis, which can be related to the development of autoimmunity, inflammation, and, in consequence, infertility.

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Section: Introductionmentioning

confidence: 99%

9-cis-retinoic acid signaling in Sertoli cells regulates their immunomodulatory function to control lymphocyte physiology and Treg differentiation

Kamińska,

Pardyak,

Lustofin

et al. 2024

Reprod Biol Endocrinol

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Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology

Cheon,

Kim,

Kim

et al. 2024

The American Journal of Pathology

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Autophagy and the pancreas: Healthy and disease states

Zhou,

Zhang,

et al. 2024

Front. Cell Dev. Biol.

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Macroautophagy/autophagy is an intracellular degradation pathway that has an important effect on both healthy and diseased pancreases. It protects the structure and function of the pancreas by maintaining organelle homeostasis and removing damaged organelles. A variety of pancreas-related diseases, such as diabetes, pancreatitis, and pancreatic cancer, are closely associated with autophagy. Genetic studies that address autophagy confirm this view. Loss of autophagy homeostasis (lack or overactivation) can lead to a series of adverse reactions, such as oxidative accumulation, increased inflammation, and cell death. There is growing evidence that stimulating or inhibiting autophagy is a potential therapeutic strategy for various pancreatic diseases. In this review, we discuss the multiple roles of autophagy in physiological and pathological conditions of the pancreas, including its role as a protective or pathogenic factor.

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Energy status regulates levels of the RAR/RXR ligand 9-cis-retinoic acid in mammalian tissues: Glucose reduces its synthesis in β-cells

Cited by 4 publications

References 90 publications

9-cis-retinoic acid signaling in Sertoli cells regulates their immunomodulatory function to control lymphocyte physiology and Treg differentiation

9-cis-retinoic acid signaling in Sertoli cells regulates their immunomodulatory function to control lymphocyte physiology and Treg differentiation

Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology

Autophagy and the pancreas: Healthy and disease states

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