title: Murine Sertoli cells promote the development of tolerogenic dendritic cells: a pivotal role of galectin-1.
abstract: 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.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xujie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Weixia
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D037483:Galectin 1 / Q000276:immunology / Q000378:metabolism*; D007108:Immune Tolerance; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012708:Sertoli Cells / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037483:Galectin 1; D018836:Inflammation Mediators; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Sertoli cells; co-culture; dendritic cells; galectin-1; immune tolerance