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J Immunol. 2014 Mar 1;192(5):2082-2090. doi: 10.4049/jimmunol.1303012. Epub 2014 Jan 31.

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

Author information

1
Lankenau Institute for Medical Research, Wynnewood PA USA.
2
New Link Genetics Corporation, Ames IA USA.
3
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia PA USA.
4
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA USA.
5
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia PA USA.
#
Contributed equally

Abstract

Rheumatoid arthritis and other autoimmune disorders are associated with altered activity of the immunomodulatory enzyme IDO. However, the precise contributions of IDO function to autoimmunity remain unclear. In this article, we examine the effect of two different IDO enzymes, IDO1 and IDO2, on the development of autoimmune arthritis in the KRN preclinical model of rheumatoid arthritis. We find that IDO2, not IDO1, is critical for arthritis development, providing direct evidence of separate in vivo functions for IDO1 and IDO2. Mice null for Ido2 display decreased joint inflammation relative to wild-type mice owing to a reduction in pathogenic autoantibodies and Ab-secreting cells. Notably, IDO2 appears to specifically mediate autoreactive responses, but not normal B cell responses, as total serum Ig levels are not altered and IDO2 knockout mice are able to mount productive Ab responses to model Ags 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 important insights into IDO2 function by defining its pathogenic contributions to autoantibody-mediated autoimmunity.

PMID:
24489090
PMCID:
PMC3947779
DOI:
10.4049/jimmunol.1303012
[Indexed for MEDLINE]
Free PMC Article
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