Screening and Identification of a Chicken Dendritic Cell Binding Peptide by Using a Phage Display Library
FRONTIERS IN IMMUNOLOGY
Authors: Ma, Sunting; Qiao, Xinyuan; Xu, Yigang; Wang, Li; Zhou, Han; Jiang, Yanping; Cui, Wen; Huang, Xuewei; Wang, Xiaona; Tang, Lijie; Li, Yijing
Abstract
Dendritic cells (DCs), as antigen-presenting cells, can initiate adaptive immune responses efficiently. Although the DC-targeting strategy has attracted more attention, relevant studies on chicken are rare. Here, specific chicken bone marrow DC-binding peptides were selected using a phage display peptide library and confirmed through ELISA, flow cytometry, fluorescence microscopy, and laser confocal microscopy. The peptide candidate SPHLHTSSPWER, named SP, was fused to the infectious bursal disease virus (IBDV) structural protein and protective antigen VP2. In vitro, the expression of DC markers (CD80, CD83, CD86, DEC205, and MHCII) and some cytokines (IFN-gamma, IL-12, TNF-alpha, IL-1 beta, IL-6, and CXCLi1) by VP2-SP-stimulated DCs was significantly higher than that by DCs treated with the VP2-control peptide at 4h (p < 0.001). In addition, an oral vaccine targeting DCs was generated using chicken-borne Lactobacillus saerimneri M11 (L. sae M11) to deliver VP2 fused with SP. Anti-IBDV mucosal and humoral immune responses were induced efficiently via oral administration, resulting in higher protective efficacy in the VP2-SP group than the VP2 group. Therefore, chicken DC targeting of IBDV protective antigen VP2 delivered by L. sae provides effective immune protection in chicken. Our study may promote research on the DC-targeting strategy to enhance the effectiveness of chicken vaccines.
Murine Sertoli cells promote the development of tolerogenic dendritic cells: a pivotal role of galectin-1
IMMUNOLOGY
Authors: Gao, Jianxin; Wang, Xujie; Wang, Yunchuan; Han, Fu; Cai, Weixia; Zhao, Bin; Li, Yan; Han, Shichao; Wu, Xue; Hu, Dahai
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.