SOCS3 ablation enhances DC-derived Th17 immune response against Candida albicans by activating IL-6/STAT3 in vitro.
Life Sci. 2019 Mar 06;:
Authors: Shi D, Yang J, Wang Q, Li D, Zheng H, Mei H, Liu W
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 γt (RORγt), 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.
PMID: 30851337 [PubMed - as supplied by publisher]