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Peptidylarginine deiminase 2 promotes T helper 17-like T cell activation and activated T cell-autonomous death (ACAD) through an endoplasmic reticulum stress and autophagy coupling mechanism.
Yang, Yi-Fang; Wang, Chuang-Ming; Hsiao, I-Hsin; Liu, Yi-Liang; Lin, Wen-Hao; Lin, Chih-Li; Hung, Hui-Chih; Liu, Guang-Yaw.
Afiliação
  • Yang YF; Department of Life Sciences, National Chung Hsing University (NCHU), Taichung, 40227, Taiwan.
  • Wang CM; Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung, 40227, Taiwan.
  • Hsiao IH; Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital (CYCH), Chia-Yi, 60002, Taiwan.
  • Liu YL; Department of Life Sciences, National Chung Hsing University (NCHU), Taichung, 40227, Taiwan.
  • Lin WH; Department of Life Sciences, National Chung Hsing University (NCHU), Taichung, 40227, Taiwan.
  • Lin CL; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
  • Hung HC; Department of Life Sciences, National Chung Hsing University (NCHU), Taichung, 40227, Taiwan.
  • Liu GY; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
Cell Mol Biol Lett ; 27(1): 19, 2022 Mar 02.
Article em En | MEDLINE | ID: mdl-35236296
ABSTRACT
Peptididylarginine deiminase type 2 (PADI2) catalyzes the conversion of arginine residues to citrulline residues on proteins. We demonstrate that PADI2 induces T cell activation and investigate how PADI2 promotes activated T cell autonomous death (ACAD). In activated Jurkat T cells, overexpression of PADI2 significantly increases citrullinated proteins and induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling, ultimately resulting in the expression of autophagy-related proteins and autophagy. PADI2 promoted autophagy and resulted in the early degradation of p62 and the light chain 3B (LC3B)-II accumulation. In Jurkat T cells, silencing the autophagy-related gene (Atg) 12 protein inhibits PADI2-mediated autophagy and promotes ER stress and apoptosis, whereas overexpression of Atg12 decreased ER stress and prolonged autophagy to promote cell survival. Additionally, PADI2 regulates T cell activation and the production of Th17 cytokines in Jurkat T cells (interleukins 6, IL-17A, IL-17F, IL-21, and IL-22). In Jurkat T cells, silencing IL-6 promotes autophagy mediated by PADI2 and inhibits PADI2-induced apoptosis, whereas silencing Beclin-1 increases the activation and survival of Th17-like T cells while decreasing autophagy and apoptosis. PADI2 silencing alleviates ER stress caused by PADI2 and decreases cytokine expression associated with Th17-like T cell activation and ACAD. We propose that PADI2 was involved in Th17 lymphocyte ACAD via a mechanism involving ER stress and autophagy that was tightly regulated by PADI2-mediated citrullination. These findings suggest that inhibiting Th17 T cell activation and the development of severe autoimmune diseases may be possible through the use of novel antagonists that specifically target PADI2.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Th17 / Estresse do Retículo Endoplasmático / Proteína-Arginina Desiminase do Tipo 2 Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Th17 / Estresse do Retículo Endoplasmático / Proteína-Arginina Desiminase do Tipo 2 Idioma: En Ano de publicação: 2022 Tipo de documento: Article