Background::Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 ( TPCN2) in SLE pathogenesis. Methods::Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). Results::TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown- TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. Conclusion::TPCN2 might be a potential protective factor against SLE.

TPCN2;Systemic lupus erythematosus;RNA sequencing analysis;Apoptosis;Cell cycle

Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China;Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 100029, China

[1]Li Keke;Xu Jingkai;Xue Ke;Yu Ruixing;Li Chengxu;Fei Wenmin;Ning Xiaoli;Han Yang;Wang Ziyi;Shu Jun;Cui Yong-.Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle)[J].中华医学杂志（英文版）,2022(04):447-455

TPCN2,lentiviruses

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