Role of inhibins in dendritic cells differentiation and maturation (P4482)

Abstract Dendritic cells (DC) play a central role establishing the balance between tolerance and immunity. Inhibins and Activins, members of the TGFβ superfamily, have been implicated in the immune system as keys regulators of cellular functions, such as proliferation, apoptosis and differentiation. Several reports have previously shown the role of Activins in DC maturation and function, however the role of their closely related cytokines, the Inhibins, in those processes remains unclear. In this study, we compare the differentiation and maturation of bone marrow derived DC (BMDC) of wild type (WT) and Inhibin α deficient (KO) female mice. Our data showed that the percentage of immature BMDC was similar between WT and KO mice but, interestingly, analysis of mature BMDC obtained after lipopolysaccharide (LPS) stimulation (mBMDC) showed a significant reduction in the surface expression of MCHII, CD80 and CD86 in KO BMDC compared to WT mBMDC. In agreement, KO mBMDC retained the morphology characteristic of iDC, consisting in cellular spreading and presence of podosome like structures. Moreover, the chemotaxis of KO mBMDC towards CCL19 was significantly diminished in comparison to WT mBMDC. Collectively, these data show an impairment in the maturation of KO BMDC mediated by LPS, suggesting a role of Inhibins in the regulation of DC mediated functions. This data contribute to a better understanding of the mechanisms involved in DC maturation and the balance between tolerance and immunity.