Intravenous immunoglobulin G (IVIg) concurrently promotes Th2 and T regulatory cell development while abrogating Th17 cells

Abstract

Abstract We aimed to further elucidate the mechanisms by which IVIg modulates the balance between Th17, Th2, and Treg. Using an OVA-driven murine model of allergic airway disease exhibiting a mixed Th17/Th2 response, we examined lung inflammation by H & E staining and histology, and performed cellular phenotyping of lung homogenates using flow cytometry. In addition, we assessed cytokine production by intracellular staining and ELISA, and performed co-culture studies. IVIg treatment reduced lung inflammation and diminished the frequency and absolute number of lung Th17 cells, IL-17A production, and neutrophilia. In contrast, the frequency and absolute number of eosinophils and basophils was increased, while IgE production was abrogated in the IVIg group. This was accompanied by a significant increase in IL-13+ and IL-5+ T cells and in IL-5 concentration in the BAL. The frequency of Foxp3+IL10+ + cells within CD4+ T cells (1.43 % ± .061 vs 2.57 % ± .30, p < .01) and IL-10 secreting dendritic cells (0.28 % ± 0.060 vs 1.20 % ± 0.27, p < .05) was augmented. We also observed an increase in the frequency of CD206 expressing macrophages, or M2 macrophages, in the IVIg group (10.81% ± 2.21 vs 19.80 % ± 1.81, p < .01). Using an in vitro DC: T cell co-culture, IVIg-treated DC inhibited IL-17A production by T cells and increased IL-13 production and Treg differentiation. In conclusion, IVIg modulates Th2/Th17/Treg balance by favoring Treg and Th2 cells while inhibiting Th17 cells. Furthermore, IVIg renders both dendritic cells and macrophages tolerogenic.