PDF(Pubmed)
Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：睾丸是一种免疫特权器官，阻止针对精子抗原和炎症的免疫反应。负责免疫耐受的睾丸细胞主要是支持细胞，形成血-睾丸屏障并产生免疫抑制因子。支持细胞通过抑制增殖和诱导淋巴细胞凋亡来预防睾丸炎症并维持免疫耐受。已显示9-顺式视黄酸（9cRA）阻断外周血淋巴细胞的离体凋亡并促进肠道中Treg细胞的分化。然而,类视黄醇信号在调节睾丸免疫特权中的作用尚不清楚.
目的：本研究的目的是确定9cRA是否，通过视黄酸受体（RAR）和视黄酸X受体（RXR），通过影响抗炎/促炎因子的分泌来控制支持细胞的免疫调节功能,淋巴细胞生理和Treg细胞分化。
方法:使用鼠支持细胞和T淋巴细胞共培养的体外模型进行实验。视黄酸受体的激动剂和拮抗剂用于抑制/刺激支持细胞中的类视黄醇信号传导。
结果：我们的结果表明，9cRA抑制了免疫抑制基因的表达，并增强了睾丸支持细胞和淋巴细胞中促炎因子的表达，增加淋巴细胞活力，降低细胞凋亡率。此外，我们发现9cRA通过RAR和RXR阻断淋巴细胞凋亡，并抑制FasL/Fas/Caspase8和Bax/Bcl-2/Caspase9途径。最后,我们已经证明，Sertoli细胞中的9cRA信号抑制Treg分化。
结论：总的来说，我们的结果表明类视黄醇信号传导负调节支持细胞的免疫特权功能，对于确保男性生育能力至关重要。9cRA抑制淋巴细胞凋亡，这可能与自身免疫的发展有关，炎症,and,因此，不孕症。
目的：本研究的目的是确定9cRA是否，通过视黄酸受体（RAR）和视黄酸X受体（RXR），通过影响抗炎/促炎因子的分泌来控制支持细胞的免疫调节功能,淋巴细胞生理和Treg细胞分化。
方法:使用鼠支持细胞和T淋巴细胞共培养的体外模型进行实验。视黄酸受体的激动剂和拮抗剂用于抑制/刺激支持细胞中的类视黄醇信号传导。
结果：我们的结果表明，9cRA抑制了免疫抑制基因的表达，并增强了睾丸支持细胞和淋巴细胞中促炎因子的表达，增加淋巴细胞活力，降低细胞凋亡率。此外，我们发现9cRA通过RAR和RXR阻断淋巴细胞凋亡，并抑制FasL/Fas/Caspase8和Bax/Bcl-2/Caspase9途径。最后,我们已经证明，Sertoli细胞中的9cRA信号抑制Treg分化。
结论：总的来说，我们的结果表明类视黄醇信号传导负调节支持细胞的免疫特权功能，对于确保男性生育能力至关重要。9cRA抑制淋巴细胞凋亡，这可能与自身免疫的发展有关，炎症,and,因此，不孕症。
