IgG derived dendritic cells can induce production of IL-17 by T cells in multiple sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Myelin-autoreactive T cells have been implicated in the initiation of an inflammatory cascade. Dendritic cells (DC) are key modulators of this immuno-pathological cascade. The interaction between immune complexes (IC) and Fc{gamma}Rs results in activation of the immune system and induction of host inflammatory responses. Otherwise, monocytes differentiate into DCs after ligation of their Fc{gamma}Rs to IgG. We investigated circulating immune complexes levels (CIC) and differentiation of monocytes onto immature dendritic cell (iDC) via Fc{gamma}R by Plate-bound human IgG in MS patients compared to healthy individuals. Our results showed that the concentration of CIC in patients with MS was significantly higher than healthy controls. Human IgG alone differentiate monocytes into DCs with a phenotype, including up-regulation of CD1b, CD86 and down-regulation of CD14. Also, the ability of LPS/MBP matured DCs in activation and cytokine production of autologous T cells was evaluated by MLR assay and ELISA. The level of IL-17 was significantly higher in MS patients when IgG derived DCs cocultured with T cells. Also, a correlation between IL-17 levels and circulating immune complexes level was observed in MS patients. Therefore, activation of Fc{gamma}R on monocytes triggers differentiation into specialized iDC with the capacity to induce auto-reactive T cells that may contribute to the pathogenesis of MS.