TY - JOUR
T1 - Type I interferons produced by resident renal cells may promote end-organ disease in autoantibody-mediated glomerulonephritis
AU - Fairhurst, Anna Marie
AU - Xie, Chun
AU - Fu, Yuyang
AU - Wang, Andrew
AU - Boudreaux, Christopher
AU - Zhou, Xin J.
AU - Cibotti, Ricardo
AU - Coyle, Anthony
AU - Connolly, John E.
AU - Wakeland, Edward K.
AU - Mohan, Chandra
PY - 2009/11/15
Y1 - 2009/11/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0900742
DO - 10.4049/jimmunol.0900742
M3 - Article
C2 - 19864599
AN - SCOPUS:77649245893
SN - 0022-1767
VL - 183
SP - 6831
EP - 6838
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -