A pathogenic role for ER stress-induced autophagy and ER chaperone GRP78/BiP in T lymphocyte systemic lupus erythematosus. Issue 2 (16th December 2014)

• Record Type: Journal Article
• Authors: Lee, Won-Seok; Sung, Myung-Soon; Lee, Eun-Gyeong; Yoo, Han-Gyul; Cheon, Yun-Hong; Chae, Han-Jung; Yoo, Wan-Hee
• Is Part Of: Journal of leukocyte biology. Volume 97:Issue 2(2015)
• Page Start: 425
• Page End: 433
• Publication Date: 2014-12-16
• Subjects: apoptosis -- SLE -- T cells; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.6A0214-097R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : ER stress induced autophagy and decreased GRP78 expression of T lymphocytes are involved in the pathogenesis of SLE and potentially important therapeutic targets. Abstract: Abnormal regulation of ER stress and apoptosis has been implicated in autoimmune disorders. Particularly, ER stress-induced autophagy and the role of GRP78, or BiP in T lymphocyte survival and death in SLE are poorly understood. This study investigated the pathogenic roles of ER stress-induced autophagy and GRP78/BiP in apoptosis of T lymphocytes. We compared spontaneous and induced autophagy and apoptosis of T lymphocytes in healthy donors and patients with SLE. The molecular mechanism of altered autophagy and apoptosis was investigated in T lymphocytes transfected with siRNA for beclin 1 and CHOP and T lymphocytes overexpressing GRP78. Decreased autophagy and increased apoptosis in response to TG-induced ER stress were observed in lupus T lymphocytes. GRP78 and ER stress-signaling molecules, such as PERK, p-eIF2 α, IRE1, and ATF6 decreased, whereas CHOP levels increased in lupus T cells in response to TG. The levels antiapoptotic molecules, Bcl-2 and Bcl-XL decreased, whereas the proapoptotic molecules, Bax and caspase 6, increased in lupus T cells. The TG-induced ER stress altered autophagy and apoptosis, which in turn, led to abnormal T cell homeostasis with increased apoptotic T cell death. We hypothesize that aberrant autophagy of T lymphocytes as a result of ER stress and decreased GRP78 expression is involved in the pathogenesis of SLE and might serve as important therapeutic targets.