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JAAD Case Reports Jun 2022
PubMed: 35600571
DOI: 10.1016/j.jdcr.2022.04.006 -
Contact Dermatitis Oct 2022
Randomized Controlled Trial
Efficacy and safety of oral alitretinoin versus oral azathioprine in patients with severe chronic hand eczema: Results from a prematurely discontinued randomized controlled trial.
Topics: Administration, Oral; Alitretinoin; Azathioprine; Chronic Disease; Dermatitis, Allergic Contact; Dermatologic Agents; Eczema; Hand Dermatoses; Humans; Treatment Outcome
PubMed: 35567385
DOI: 10.1111/cod.14161 -
Reproductive Biology and Endocrinology... Jun 2024Testis is an immune privileged organ, which prevents the immune response against sperm antigens and inflammation. Testicular cells responsible for immune tolerance are...
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.
Topics: Male; Animals; Sertoli Cells; T-Lymphocytes, Regulatory; Signal Transduction; Mice; Tretinoin; Cell Differentiation; Alitretinoin; Receptors, Retinoic Acid; Apoptosis; Coculture Techniques; Mice, Inbred C57BL; Cells, Cultured; Immunomodulation
PubMed: 38926848
DOI: 10.1186/s12958-024-01246-2 -
Frontiers in Immunology 2021The retinoid X receptor agonist bexarotene promotes remyelination in patients with multiple sclerosis. Murine studies have also demonstrated that RXR agonists have...
The retinoid X receptor agonist bexarotene promotes remyelination in patients with multiple sclerosis. Murine studies have also demonstrated that RXR agonists have anti-inflammatory effects by enhancing the ability of all-trans-retinoic acid (RA) to promote T-regulatory cell (Treg) induction and reduce Th17 differentiation By stimulating human naïve CD4 T-cells in the presence of Treg or Th17 skewing cytokines, we show that bexarotene also tips the human Treg/Th17 axis in favor of Treg induction, but unlike murine cells this occurs independently of RA and retinoic acid receptor signaling. Tregs induced in the presence of bexarotene express canonical markers of T-regulation and are functionally suppressive Circulating Treg numbers did not increase in the blood of trial patients receiving bexarotene; we believe this is because Treg induction is likely to occur within tissues. These findings lend support to developing RXR agonists as treatments of autoimmune diseases, in particular multiple sclerosis.
Topics: Adult; Alitretinoin; Bexarotene; CD4-Positive T-Lymphocytes; Cells, Cultured; Clinical Trials as Topic; Fatty Acids, Unsaturated; Female; Forkhead Transcription Factors; Humans; Leukocytes, Mononuclear; Lymphopoiesis; Middle Aged; Remyelination; Retinoid X Receptors; T-Lymphocytes, Regulatory; Tetrahydronaphthalenes; Th17 Cells
PubMed: 34447379
DOI: 10.3389/fimmu.2021.712241 -
Annals of Dermatology Aug 2019
PubMed: 33911675
DOI: 10.5021/ad.2019.31.S.S1