Type I interferons produced by resident renal cells may promote end-organ disease in autoantibody-mediated glomerulonephritis.
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.
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8884, USA.
Anna-Marie
AM
Fairhurst
Chun
C
Xie
Yuyang
Y
Fu
Andrew
A
Wang
Christopher
C
Boudreaux
Xin J
XJ
Zhou
Ricardo
R
Cibotti
Anthony
A
Coyle
John E
JE
Connolly
Edward K
EK
Wakeland
Chandra
C
Mohan
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins
D000998:Antiviral Agents; D001323:Autoantibodies; D016207:Cytokines; D007370:Interferon Type I; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta