HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900742v1 183/10/6831    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Fairhurst, A.-M. Articles by Mohan, C. PubMed PubMed Citation Articles by Fairhurst, A.-M. Articles by Mohan, C.

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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.

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

⁵ Abbreviations used in this paper: SLE, systemic lupus erythematosus; IFN-I, type I IFN; BUN, blood urea nitrogen; GBM, glomerular basement membrane; ADV, adenovirus.