TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wen, Y; Rudemiller, NP; Zhang, J; Robinette, T; Lu, X; Ren, J; Privratsky, JR; Nedospasov, SA; Crowley, SD

Published Date

  • January 1, 2020

Published In

Volume / Issue

  • 318 / 1

Start / End Page

  • F107 - F116

PubMed ID

  • 31736350

Pubmed Central ID

  • PMC6985827

Electronic International Standard Serial Number (EISSN)

  • 1522-1466

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00347.2019


  • eng

Conference Location

  • United States