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AT2 Receptor Activation Induces Treg Cells and Mitigates Renal Ischemic Injury
Author(s) -
Ali Riyasat,
Patel Sanket,
Hussain Tahir
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02046
Subject(s) - kidney , immune system , foxp3 , proinflammatory cytokine , acute kidney injury , medicine , infiltration (hvac) , kidney disease , creatinine , renal ischemia , inflammation , ischemia , endocrinology , immunology , reperfusion injury , physics , thermodynamics
Kidney infiltrating immune cells such as monocytes, neutrophils, and T‐cells play critical roles in renal ischemia‐reperfusion (IR) injury and repair. Recently, angiotensin AT2R has been implicated in protecting kidney against injury and monocytes infiltration, particularly in chronic kidney disease. However, the role of AT2R in IR injury and repair phases, and T‐cell modulation is unknown. To address this question, Sprague‐Dawley rats were administered with the AT2R agonist C21 (0.3 mg/kg, i.p.) two hour before 30‐minute bilateral renal ischemia. IR caused an early (2h post‐ischemia) renal functional injury as indicated by elevated proteinuria, blood urea nitrogen and plasma creatinine, and enhanced immune cells (T‐cells and CD4 T‐cells) infiltration and levels of the proinflammatory cytokines TNF‐α and IL‐6. The C21 treatment reversed these changes and increased the anti‐inflammatory IL‐10 level. During the repair phase at day 3 and 5, renal functional injury and T cells infiltration in IR and IR+C21 returned to normal as sham controls. However, high percentages of CD4+FoxP3+ (Tregs, known for their role in repair), and CD4+IL‐10+ cells in the kidney were observed in IR+C21 group compared with IR control. These data indicate that the AT2R activation protects the kidney against IR injury and immune cell infiltration in the early phase and modulates CD4 T‐cells towards Tregs phenotype, which may have long‐term beneficial effects on kidney function.