Stimulating Type 1 Angiotensin Receptors on T Lymphocytes Attenuates Renal Fibrosis.

In this study, mice with T-cell-specific deletion of the dominant murine AT1 receptor isoform Lck-Cre Agtraflox/flox [total knockout (TKO)] and wild-type (WT) controls were subjected to the unilateral ureteral obstruction model of kidney fibrosis. Compared with WT controls, obstructed kidneys from TKO mice at day 14 had increased collagen 1 deposition. CD4+ T cells, CD11b+Ly6Chi myeloid cells, and mRNA levels of Th1 inflammatory cytokines are elevated in obstructed TKO kidneys, suggesting that augmented Th1 responses in the TKO mice may exaggerate renal fibrosis by driving proinflammatory macrophage differentiation. In turn, T-bet deficient (T-bet knockout) mice lacking Th1 responses have attenuated collagen deposition after unilateral ureteral obstruction. We conclude that activating the AT1 receptor on T cells mitigates renal fibrogenesis by inhibiting Th1 differentiation and renal accumulation of profibrotic macrophages. PMID: 31000207 [PubMed - as supplied by publisher]
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research