Loss of IL-10 Promotes Differentiation of Microglia to a M1 Phenotype

Microglia represent the primary resident immune cells of the central nervous system (CNS) and modulate local immune responses. Depending on their physiological functions, microglia can be classified into pro- (M1) and anti-inflammatory (M2) phenotype. Interleukin (IL)-10 is an important modulator of neuronal homeostasis, with anti-inflammatory and neuroprotective functions, and can be released by microglia. Here, we investigated how IL-10 deficiency affected the M1/2 polarization of primary microglia upon lipopolysaccharide (LPS) stimulation in vitro. Microglia phenotypes were analyzed via flow cytometry. Cytokine and chemokine secretion were examined by ELISA and bead-based multiplex LEGENDplex (TM). Our results showed that genetic depletion of IL-10 led to elevated M1 like phenotype (CD86+ CD206-) under pro-inflammatory conditions associated with increased frequency of IL-6+, TNF-alpha+ cells and enhanced release of several pro-inflammatory chemokines. Absence of IL-10 led to an attenuated M2 like phenotype (CD86- CD206+) and a reduced secretion of TGF-beta 1 upon LPS stimulation. In conclusion, IL-10 deficiency may promote the polarization of microglia into M1-prone phenotype under pro-inflammatory conditions.