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Type I Interferons Produced by Resident Renal Cells May Promote End-Organ Disease in Autoantibody-Mediated Glomerulonephritis¹

Anna-Marie Fairhurst,² Chun Xie,^2* Yuyang Fu,^* Andrew Wang, Christopher Boudreaux, Xin J. Zhou, Ricardo Cibotti, Anthony Coyle, John E. Connolly,^¶ Edward K. Wakeland,³ and Chandra Mohan^34*

*Departments of Internal Medicine, Immunology, and Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Medimmune, Gaithersburg, MD 20878; and ^¶Baylor Institute for Immunology Research, Dallas, TX 75204

Increased Type I IFNs or IFN-I have been associated with human systemic lupus erythematosus. Interestingly augmenting or negating IFN-I activity in murine lupus not only modulates systemic autoimmunity, but also impacts lupus nephritis, suggesting that IFN-I may be acting at the level of the end-organ. We find resident renal cells to be a dominant source of IFN-I in an experimental model of autoantibody-induced nephritis. In this model, augmenting IFN-I amplified antibody-triggered nephritis, whereas ablating IFN-I activity ameliorated disease. One mechanism through which increased IFN-I drives immune-mediated nephritis might be operative through increased recruitment of inflammatory monocytes and neutrophils, though this hypothesis needs further validation. Collectively, these studies indicate that an important contribution of IFN-I toward the disease pathology seen in systemic autoimmunity may be exercised at the level of the end-organ.

⁴ Address correspondence and reprint requests to Dr. Chandra Mohan, Department of Internal Medicine/Rheumatology, University of Texas Southwestern Medical Center, Mail Code 8884, Y8.204, 5323 Harry Hines Boulevard, Dallas, TX 75390-8884. E-mail address: Chandra.mohan{at}utsouthwestern.edu

¹ This work was supported by funding from the National Institutes of Health, Medimmune and the Alliance for Lupus Research.

² A.-M.F. and C.X. contributed equally to this article.

³ E.K.W. and C.M. are co-senior authors.