TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis
| Autor: | Yi Wen, Jiandong Zhang, Sergei A. Nedospasov, Taylor J. Robinette, Xiaohan Lu, Jamie R. Privratsky, Jiafa Ren, Nathan P. Rudemiller, Steven D. Crowley |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology T-Lymphocytes medicine.medical_treatment 030232 urology & nephrology Kidney Nephrotoxicity Mice 03 medical and health sciences Glomerulonephritis 0302 clinical medicine Renal injury Fibrosis medicine Animals Mice Knockout Tumor Necrosis Factor-alpha business.industry Interleukin-17 T lymphocyte medicine.disease Disease Models Animal 030104 developmental biology Cytokine Immunology Kidney inflammation business Nephritis Research Article |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 1931-857X |
| Popis: | Nephrotoxic serum nephritis (NTN) models immune-mediated human glomerulonephritis and culminates in kidney inflammation and fibrosis, a process regulated by T lymphocytes. TNF-α is a key proinflammatory cytokine that contributes to diverse forms of renal injury. Therefore, we posited that TNF-α from T lymphocytes may contribute to NTN pathogenesis. Here, mice with T cell-specific deletion of TNF-α (TNF TKO) and wild-type (WT) control mice were subjected to the NTN model. At 14 days after NTN, kidney injury and fibrosis were increased in kidneys from TNF TKO mice compared with WT mice. PD1+CD4+ T cell numbers and mRNA levels of IL-17A were elevated in NTN kidneys of TNF TKO mice, suggesting that augmented local T helper 17 lymphocyte responses in the TNF TKO kidney may exaggerate renal injury and fibrosis. In turn, we found increased accumulation of neutrophils in TNF TKO kidneys during NTN. We conclude that TNF-α production in T lymphocytes mitigates NTN-induced kidney injury and fibrosis by inhibiting renal T helper 17 lymphocyte responses and infiltration of neutrophils. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|