Monocytes promote the formation of autoreactive Th17 cells in inflammatory arthritis (101.23)

Abstract

Abstract Th17 cells have been implicated in a number of autoimmune diseases and their animal models including inflammatory arthritis. How these cells arise in the context of autoimmunity is not well understood. We recently described a mouse model of autoimmune arthritis in which mice expressing influenza hemagglutinin (HA) as a self-antigen under the control of a MHC Class II promoter (HACII), and co-expressing an HA-specific CD4+ TCR (TS1), spontaneously develop inflammatory arthritis by an IL-17-dependent mechanism. Here we have used these TS1xHACII mice to investigate the role of specific cell types in the activation of autoreactive CD4+ Th17 cells. We have found that monocytes are selectively enriched in the spleens and LNs of arthritic TS1xHACII mice relative to mice expressing the HACII transgene alone. Moreover, monocytes purified from the spleens of arthritic TS1xHACII and HACII mice had profound differences in their abilities to activate HA-specific T cells in vitro: monocytes from HACII mice were potent inducers of Th1 cells, whereas those from TS1xHACII mice were significantly more efficient at inducing Th17 cells. Monocytes from TS1xHACII mice also had an enhanced capacity to induce Th17 cells relative to B cells and cDCs isolated in parallel from the same organs. Collectively, these data suggest that monocytes can play an important role in the development of Th17 cells in vivo, and can participate in an autoimmune response that results in inflammatory arthritis.