Murine Sertoli cells promote the development of tolerogenic dendritic cells: a pivotal role of galectin-1
Murine Sertoli cells promote the development of tolerogenic dendritic cells: a pivotal role of galectin-1
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小鼠支持细胞促进耐受性树突状细胞的发育：galectin-1 的关键作用。
DOI：
10.1111/imm.12598
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发表时间：
2016-07-01
期刊：
影响因子：
6.4
通讯作者：
Hu, Dahai
中科院分区：
文献类型：
--
作者：
Gao, Jianxin;Wang, Xujie;Hu, Dahai
支持细胞（SCs）具有固有的免疫抑制特性，是哺乳动物睾丸免疫特权状态的主要贡献者。据报道，SCs可以抑制B细胞、T细胞和自然杀伤细胞的活化，但不能抑制树突状细胞（DCs）的活化。在此，我们提供的证据表明，与SCs共培养导致DC持续不成熟状态，其特征是表面分子I-A/E、CD80、CD83、CD86、CCR7和CD11c下调，以及促炎细胞因子的产生减少。SC-DCs表现出低免疫原性和增强的免疫调节功能，包括抑制t细胞增殖和促进Foxp3（+）调节性t细胞发育。在机制上，SC-DCs抑制了p38、细胞外信号调节激酶1/2、信号转导和转录激活因子3的激活。更重要的是，我们证明了sc分泌的半乳糖凝集素-1在功能耐受性sc - dc的分化中起着关键作用。这些发现进一步支持了SCs在维持睾丸免疫特权环境中的作用，并提供了一种获得耐受性dc的新方法，这可能导致治疗免疫致病性疾病的替代治疗策略。
Sertoli cells (SCs) possess inherent immunosuppressive properties and are major contributors to the immunoprivileged status of mammalian testis. SCs have been reported to inhibit the activation of B cells, T cells and natural killer cells but not dendritic cells (DCs). Herein, we present evidence that co-culture with SCs results in a persistent state of DC immaturity characterized by down-regulation of the surface molecules I-A/E, CD80, CD83, CD86, CCR7 and CD11c, as well as reduced production of pro-inflammatory cytokines. SC-conditioned DCs (SC-DCs) displayed low immunogenicity and enhanced immunoregulatory functions, including the inhibition of T-cell proliferation and the promotion of Foxp3(+) regulatory T-cell development. Mechanistically, the activation of p38, extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 3 was suppressed in SC-DCs. More importantly, we demonstrate that galectin-1 secreted by SCs plays a pivotal role in the differentiation of functionally tolerogenic SC-DCs. These findings further support the role of SCs in maintaining the immunoprivileged environment of the testis and provide a novel approach to derive tolerogenic DCs, which may lead to alternative therapeutic strategies for the treatment of immunopathogenic diseases.