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RANTES Deficiency Attenuates Autoantibody-Induced Glomerulonephritis

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Abstract

Experimental autoimmune nephritis in mice and spontaneous lupus nephritis are both associated with elevated expression of several chemokines in the kidneys. Nevertheless, the role that different chemokines play in mediating renal inflammation is far from complete. This study focuses on elucidating the functional role of RANTES, a chemokine that has been noted to be hyper-expressed within the kidneys, both in experimental renal disease as well as in spontaneous lupus nephritis. To elucidate if RANTES was essential for immune-mediated glomerulonephritis, DBA/1 mice that are highly sensitive to nephrotoxic serum nephritis were rendered RANTES-deficient and then tested for disease susceptibility. Nephritis-sensitive DBA/1 mice expressed more RANTES within the diseased kidneys. Compared to wild-type DBA/1 mice, RANTES-deficient DBA/1 mice developed significantly less proteinuria, azotemia, and renal inflammation, with reduced crescent formation and tubulo-interstitial nephritis. These findings indicate that RANTES ablation attenuates immune-mediated nephritis and suggest that this chemokine could be a potential therapeutic target in these diseases.

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Abbreviations

NTN:

Nephrotoxic serum nephritis

GBM:

Glomerular basement membrane

NTS:

Nephrotoxic sera

GN:

Glomerulonephritis

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Mail Code 8884, Y8.212, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8884, USA

    Chun Xie, Kui Liu, Yuyang Fu, Xiangmei Qin, Geetha Jonnala, Xin J. Zhou & Chandra Mohan

  2. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Tao Wang, Hong W. Wang & Xin J. Zhou

  3. Division of Rheumatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Michael Maldonado

Authors
  1. Chun Xie
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  2. Kui Liu
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  3. Yuyang Fu
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  4. Xiangmei Qin
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  7. Hong W. Wang
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  8. Michael Maldonado
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  9. Xin J. Zhou
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  10. Chandra Mohan
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Corresponding authors

Correspondence to Xin J. Zhou or Chandra Mohan.

Additional information

This work is supported in part by the NIH grants RO1 AR50812, as well as the National Arthritis Foundation.

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Xie, C., Liu, K., Fu, Y. et al. RANTES Deficiency Attenuates Autoantibody-Induced Glomerulonephritis. J Clin Immunol 31, 128–135 (2011). https://doi.org/10.1007/s10875-010-9470-x

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  • DOI: https://doi.org/10.1007/s10875-010-9470-x

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