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Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction
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Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction
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Journal Article
Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction
2010
Overview
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.
Publisher
Elsevier Inc,Nature Publishing Group,Elsevier Limited
Subject
/ Biological and medical sciences
/ CD4-Positive T-Lymphocytes - physiology
/ fibrosis
/ Fibrosis - prevention & control
/ Homeodomain Proteins - genetics
/ Kidney Diseases - immunology
/ Kidneys
/ Lymphocyte Depletion - methods
/ Mice
/ Nephrology. Urinary tract diseases
/ Ureteral Obstruction - complications
/ Ureteral Obstruction - pathology
/ Urinary system involvement in other diseases. Miscellaneous
