IL‐17 augment type I IFN‐mediated antibody production in BXD2 autoimmune mouse

Abstract

Type I IFN and IL‐17 are thought to induce distinct autoimmune diseases. However, patients with Th17‐mediated diseases could also present with a type I IFN signature, suggestive that IL‐17 and type I IFN may not be mutually exclusive for the induction of disease. As a novel model of autoimmune disease, BXD2 mice exhibit an increased presence of both IL‐17 and type I IFN. BXD2 mice displayed significantly increased serum IL‐17 (5–6 fold), and Th17 population in the spleen of BXD2 mice relative to that of non‐autoimmune mice (14% vs. 0.1%). Blood mononuclear cells showed increased type I IFN message levels (6‐fold), and treatment with CpG increased serum IFN‐á (5–50‐fold) in BXD2 mice. Confocal microscopy showed the presence of an increased population (2–4 fold) of plasmacytoid dendritic cells (pDCs) that primarily produce IFN‐á in BXD2 spleen (~80% of IFN‐á+ cells are pDCs in BXD2 mouse). When treated with CpG, serum IFN‐á (2–3 fold) was decreased in mice in which IL‐17 signaling was disrupted compared to normal BXD2 and B6 mice. In vivo blocking of IFN‐á in NP‐CGG immunized BXD2 mouse also decreased antibody serum titers to pre‐immunization levels, demonstrating that IFN‐á is essential to antibody formation. Our study indicates that IL‐17 signaling promotes IFN‐á expression and thereby may provide a novel pathway by which IL‐17 promote antibody production through type I IFN.