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Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction

Lookup NU author(s): Dr Amy Fearn, Professor Neil SheerinORCiD

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Abstract

Tubulointerstitial fibrosis is a common consequence of a diverse range of kidney diseases that lead to end-stage renal failure. The degree of fibrosis is related to leukocyte infiltration. Here, we determined the role of different T cell populations on renal fibrosis in the well-characterized mouse model of unilateral ureteric obstruction. Depletion of CD4(+) T cells in wild-type mice with a monoclonal antibody significantly reduced the amount of interstitial expansion and collagen deposition after 2 weeks of obstruction. Reconstitution of lymphopenic RAG knockout mice with purified CD4(+) but not CD8(+) T cells, prior to ureteric obstruction, resulted in a significant increase in interstitial expansion and collagen deposition. Wild-type mice had significantly greater interstitial expansion and collagen deposition compared with lymphopenic RAG(-/-) mice, following ureteric obstruction; however, macrophage infiltration was equivalent in all groups. Thus, our results suggest that renal injury with subsequent fibrosis is likely to be a multifactorial process, with different arms of the immune system involved at different stages. In this ureteric obstruction model, we found a critical role for CD4(+) T cells in kidney fibrosis. These cells could be a potential target of therapeutic intervention to prevent excessive fibrosis and loss of function due to renal injury. Kidney International (2010) 78, 351-362; doi:10.1038/ki.2010.177;published online 16 June 2010


Publication metadata

Author(s): Tapmeier TT, Fearn A, Brown K, Chowdhury P, Sacks SH, Sheerin NS, Wong W

Publication type: Article

Publication status: Published

Journal: Kidney International

Year: 2010

Volume: 78

Issue: 4

Pages: 351-362

Print publication date: 01/08/2010

ISSN (print): 0085-2538

ISSN (electronic): 1523-1755

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ki.2010.177

DOI: 10.1038/ki.2010.177


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