دورية أكاديمية
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
| العنوان: | 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 |
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| المؤلفون: | Yi-Fang Yang, Chuang-Ming Wang, I.-Hsin Hsiao, Yi-Liang Liu, Wen-Hao Lin, Chih-Li Lin, Hui-Chih Hung, Guang-Yaw Liu |
| المصدر: | Cellular & Molecular Biology Letters, Vol 27, Iss 1, Pp 1-25 (2022) |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | Peptidylarginine deiminase 2, Cytokines, Activated T cell-autonomous death, Endoplasmic reticulum stress, Autophagy, Cytology, QH573-671 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1425-8153 1689-1392 |
| العلاقة: | https://doaj.org/toc/1425-8153Test; https://doaj.org/toc/1689-1392Test |
| DOI: | 10.1186/s11658-022-00312-0 |
| الوصول الحر: | https://doaj.org/article/802dbea7a5d24e36b93b82939b615eb4Test |
| رقم الانضمام: | edsdoj.802dbea7a5d24e36b93b82939b615eb4 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14258153 16891392 |
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| DOI: | 10.1186/s11658-022-00312-0 |