IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis1

• Published in: The Journal of immunology (1950) 2014-01, Vol.192 (5), p.2082-2090
• Main Authors: Merlo, Lauren M.F., Pigott, Elizabeth, DuHadaway, James B., Grabler, Samantha, Metz, Richard, Prendergast, George C., Mandik-Nayak, Laura
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1303012

Rheumatoid arthritis (RA) and other autoimmune disorders are associated with altered activity of the immunomodulatory enzyme indoleamine-2,3-dioxygenase (IDO). However, the precise contributions of IDO function to autoimmunity remain unclear. Here, we examine the effect of two different IDO enzymes, IDO1 and IDO2, on the development of autoimmune arthritis in the KRN preclinical model of RA. We find that IDO2, not IDO1, is critical for arthritis development, providing the first direct evidence of separate in vivo functions for IDO1 and IDO2. Mice null for Ido2 display decreased joint inflammation relative to wild-type mice due to a reduction in pathogenic autoantibodies and antibody secreting cells. Notably, IDO2 appears to specifically mediate autoreactive, but not normal B cell responses, as total serum Ig levels are not altered and IDO2 ko mice are able to mount productive antibody responses to model antigens in vitro and in vivo . Reciprocal adoptive transfer studies confirm that autoantibody production and arthritis are modulated by IDO2 expression in a cell type extrinsic to the T cell. Taken together, our results provide the first insights into IDO2 function by defining its pathogenic contributions to autoantibody-mediated autoimmunity.