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Clinical Trial
. 2015 Feb;97(2):425-33.
doi: 10.1189/jlb.6A0214-097R. Epub 2014 Dec 16.

A pathogenic role for ER stress-induced autophagy and ER chaperone GRP78/BiP in T lymphocyte systemic lupus erythematosus

Won-Seok Lee  1 , Myung-Soon Sung  1 , Eun-Gyeong Lee  1 , Han-Gyul Yoo  1 , Yun-Hong Cheon  1 , Han-Jung Chae  1 , Wan-Hee Yoo  2
Affiliations
Clinical Trial

A pathogenic role for ER stress-induced autophagy and ER chaperone GRP78/BiP in T lymphocyte systemic lupus erythematosus

Won-Seok Lee et al. J Leukoc Biol. 2015 Feb.

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-eIF2α, 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.

Keywords: SLE; T cells; apoptosis.

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