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

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Duke University Medical Center
  • Lomonosov Moscow State University

Details

Original languageEnglish (US)
Pages (from-to)F107-F116
JournalAmerican Journal of Physiology - Renal Physiology
Volume318
Issue number1
StatusPublished - Jan 1 2020
Peer-reviewedYes

Abstract

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.

    Research areas

  • Cytokine, Nephritis, T lymphocyte, Tumor necrosis factor-α

Citation formats

APA

Wen, Y., Rudemiller, N. P., Zhang, J., Robinette, T., Lu, X., Ren, J., ... Crowley, S. D. (2020). TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis. American Journal of Physiology - Renal Physiology, 318(1), F107-F116. https://doi.org/10.1152/ajprenal.00347.2019

Harvard

Wen, Y, Rudemiller, NP, Zhang, J, Robinette, T, Lu, X, Ren, J, Privratsky, JR, Nedospasov, SA & Crowley, SD 2020, 'TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis', American Journal of Physiology - Renal Physiology, vol. 318, no. 1, pp. F107-F116. https://doi.org/10.1152/ajprenal.00347.2019