SOCS3 ablation enhances DC-derived Th17 immune response against Candida albicans by activating IL-6/STAT3 in vitro

LIFE SCIENCES

卷:222

Article

Shi, Dongmei^1,2  Yang, Jia³  Wang, Qiong^4,5,6  Li, Dongmei⁷  Zheng, Hailin^4,5,6  Mei, Huan^4,5,6  Liu, Weida^4,5,6 

[1] Jining 1 Peoples Hosp, Dept Dermatol, 6 Jiankang Rd, Jining 272001, Shandong, Peoples R China

[2] Jining 1 Peoples Hosp, Lab Med Mycol, Jining, Shandong, Peoples R China

[3] Zhejiang Prov Hosp TCM, Hangzhou, Zhejiang, Peoples R China

[4] Chinese Acad Med Sci, Inst Dermatol, Dept Mycol, Nanjing, Jiangsu, Peoples R China

[5] Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China

[6] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China

[7] Georgetown Univ, Med Ctr, Washington, DC 20007 USA

关键词: Candida albicans;    Dendritic cells;    Suppressor of cytokine signaling-3;    T help cell 17 (Th17);   

DOI  :  10.1016/j.lfs.2019.03.009

来源: Elsevier

【 摘 要 】

Aims: Enhancing the potency of dendritic cells (DCs) by downregulating negative immunoregulatory pathways may provide immunotherapeutic possibilities against candidiasis. Main methods: In this study, a si-RNA method is used to repress expression of the cytokine signaling-3 suppressor (SOCS3) in murine bone marrow-DCs, and then the maturation of DCs and the subsequent T-cell response after exposure to C. albicans are monitored in vitro. Key findings: Along with a higher expression of the DC maturation markers CD40, CD86 and MHC-II, IL-6/STAT3 is markedly upregulated in the SOCS3 siRNA-treated DCs after exposure to C. albicans as compared with control DCs. In response to DCs maturation, CD4(+) T cells have an increased expression of Th17 cell markers - including the retinoic acid-related orphan nuclear hormone receptors gamma t (ROR gamma t), IL-17A and IL-23R - and increased release of IL-17. We note that this enhanced Th17 cell differentiation induced by siSOCS3-treated DCs in presence of C. albicans can be partly offset when anti-IL-6 antibody is added into the co-culture. Significance: As with SOCS1 in our previous report, suppression of SOCS3 alone also has the potential to fully activate DCs maturation. However, while SOCS1 knockdown in DCs during C. albicans infection specifically augments Th1 differentiation, SOCS3 silencing particularly increases Th17 differentiation.

【 授权许可】

Free