期刊
IMMUNOLOGY
卷 148, 期 3, 页码 253-265出版社
WILEY-BLACKWELL
DOI: 10.1111/imm.12598
关键词
co-culture; dendritic cells; galectin-1; immune tolerance; Sertoli cells
类别
资金
- National Natural Science Foundation of China [81301632, 81401593]
- National Natural Science Foundation of Shannxi Province [2014JM4179]
- Scientific Research Prom Xijing Hospital [XJZT12D01]
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.
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