TIPE2 Play a Negative Role in TLR4-Mediated Autoimmune T Helper 17 Cell Responses in Patients with Myasthenia Gravis.
Th17-related cytokines have been suggested to play a crucial role in myasthenia gravis (MG) pathogenesis.The tumor necrosis factor (TNF)-α-induced protein 8-like-2 (TNFAIP8L2 or TIPE2), is a newly identified member of the tumor necrosis TNFAIP8 family which is an essential negative regulator of both innate and adaptive immunity. In the present study, the expression of TIPE2 mRNA and protein in peripheral blood mononuclear cells (PBMC) from healthy and MG subjects were detected by Real-time PCR and Western blotting.The serum IL-6, IL-17 and IL-21 levels were tested by ELISA. Furthermore, PBMC from MG patients were purified and stimulated with LPS (TLR4 agonist) with or without transfection of TIPE2 expressing adenovirus, then the expression of TIPE2 and Th17-specific transcriptional factor RORγt and the IL-6, IL-17 and IL-21 levels of supernatant were analized. Our data demonstrated that the expression of TIPE2 mRNA and protein was reduced in MG compared with normal controls, with lower expression in generalized patients than in ocular ones. Furthermore, TIPE2 mRNA presents a significantly negative correlation with the serum levels of IL-6, IL-17 and IL-21 in either generalized patients or ocular patients. In cultured MG PBMC, TLR4 activation led to the down-regulation of TIPE2, while the expression of RORγt and production of IL-6, IL-17 and IL-21 were significantly increased. However, when TIPE2 was overexpressed, these TLR4 activation-induced effects were significantly abrogated. Overall, our results indicated for the first time that TIPE2 may participate in the development of MG through negatively regulation of TLR4-mediated autoimmune T helper 17 cell responses.
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. zy20037416@163.com.
Yong
Y
Zhang
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Zhen
Z
Shao
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Xiuying
X
Zhang
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Xiao
X
Jia
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Yan
Y
Xia
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Yanyan
Y
Zhang
Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
Ning
N
Xin
Department of Emergency Medicine, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
Mingfeng
M
Guo
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Jing
J
Chen
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
ShuangShuang
S
Zheng
Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
YuZhong
Y
Wang
Department of Pathogenic Biology and Lab of Infection and Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
Linlin
L
Fu
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Ruiguo
R
Dong
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Chenghua
C
Xiao
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
Deqin
D
Geng
Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. yonhailiumg@163.com.
Yonghai
Y
Liu
D000328:Adult; D000368:Aged; D015551:Autoimmunity / Q000276:immunology*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; C495345:TLR4 protein, human; C552057:TNFAIP8L2 protein, human; D051197:Toll-Like Receptor 4
Myasthenia gravis; TIPE2; TLR4; Th17-related cytokines