Deficiency in WDFY4 reduces the number of CD8+ T cells via reactive oxygen species-induced apoptosis. (November 2021)

• Record Type: Journal Article
• Authors: Li, Yan; Li, Jiangxia; Yuan, Qianqian; Bian, Xianli; Long, Feng; Duan, Ruonan; Gao, Fei; Gao, Shang; Wei, Shijun; Wang, Anran; Liu, Ai; Li, Xi; Sun, Wenjie; Liu, Qiji
• Is Part Of: Molecular immunology. Volume 139(2021)
• Page Start: 131
• Page End: 138
• Publication Date: 2021-11
• Subjects: WDFY4 WD repeat and FYVE domain containing 4 -- SLE systemic lupus erythematosus -- cDC1 conventional type 1 dendritic cell -- CKO conditional knockout -- DN double-negative stage -- DP double positive stage -- SP spleen -- LN lymph node -- ROS reactive oxygen species -- Jurkat cell human T lymphocytes; WDFY4 -- CD8+ T cells -- Reactive oxygen species -- Apoptosis; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.08.022
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: WDFY4 modulates T cell fate via reactive oxygen species-induced apoptosis. WDFY4 participates in apoptosis via the p53 and ERK pathways. Wdfy4 influences the proliferation of CD8 + T cells. Abstract: WDFY4 (WD repeat and FYVE domain-containing 4) is a susceptibility gene involved in several autoimmune diseases and plays an important role in the immune system. However, it is not clear how WDFY4 affects T cells. We have generated a Wdfy4 -knockout mouse and found that selective deficiency of Wdfy4 in T cells led to a reduction in the number of CD8 + T cells in the periphery, thus promoting tumor growth when mice were challenged with a transplantable tumor. Moreover, conditional ablation of Wdfy4 in T cells enhanced the apoptosis of CD8 + T cells and increased the intracellular levels of reactive oxygen species accompanied by the upregulation of Nox2 . Mechanistically, the decrease in the CD8 + T-cell numbers in Wdfy4 -knockout mice was associated with activation of the p53 pathway and inhibition of the extracellular signal-regulated kinase pathway. In addition, WDFY4 participated in cell proliferation. In conclusion, our results elucidate the biological role of WDFY4 in apoptosis and establish a link between WDFY4 and T cells.