SOCS3 Regulates Dectin-2-Induced Inflammation in PBMCs of Diabetic Patients

Abstract

Abstract The C-type lectin receptors (CLRs) Dectin-1 and Dectin-2 are involved in several innate immune responses and are expressed mainly in dendritic cells, monocytes, and macrophages. This study aims to evaluate the expression and function of Dectin-2 in peripheral blood mononuclear cells (PBMCs) isolated from diabetic patients and non-diabetic controls. Our results show that Dectin-2 expression was the highest in monocytes compared with other leukocyte subpopulations. The expression of Dectin-2 was also found to be significantly higher in T2D patients monocytes compared with non-diabetic controls. The expression of Dectin-2 was found to be positively correlated with markers of glucose homeostasis, including HOMA-IR and HbA1c. Interestingly, SOCS3, a negative regulator of inflammation, was expressed significantly lower in the PBMCs of T2D patients. Moreover, SOCS3 expression was negatively correlated with Dectin-2 expression level. Further analysis of inflammatory signaling pathways showed a persistent activation of the Dectin-2-Syk-NFkB pathway that was instigated by the diminished expression of SOCS3. Dectin-2 activation failed to induce SOCS3 expression and suppress subsequent inflammatory responses in the PBMCs of diabetic patients. siRNA-mediated knockdown of SOCS3 in PBMCs displayed a similar inflammatory phenotype to diabetic PBMCs when exposed to Dectin-2 ligands. Altogether, our findings suggest that elevated Dectin-2 and its relationship with SOCS3 could be involved in the abnormal immune response observed in T2D patients. This work was supported and funded by the Kuwait University Research Grant No. [SL01/21] and by the Kuwait Foundation for the Advancement of Sciences (KFAS) grant No. (RA MoH-2022-002).