A Role of TREX1 in Immune Regulation and Human Diseases
ZHANG Si-Tong, DU He-Kang, CHEN Qi*
Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, Fujian Normal University Qishan Campus, Fuzhou 350117, China
Abstract：Three prime repair exonuclease 1 (TREX1), also known as DNase Ⅲ, is a major 3'-5' restriction exonuclease in most of tissues and cell types of the mammals. The exonuclease activity of TREX1 plays an essential role in maintaining the immune tolerance of the innate immune system, which avoids the excessive activation of the innate immune system and massive production of auto-antibodies induced by the abnormal accumulation of cytosolic DNA. cGAS-STING signaling was identified as an important innate immune response to pathogens and maintained cellular environmental homeostasis. TREX1 prevents occasional leakage of nuclear DNA into the cytosol, which activates cGAS and triggers the downstream type I interferons cascade. Mutations of human TREX1 cause a series of autoimmune diseases, such as Aicardi-Goutières syndrome (AGS), Familial chilblain lupus (FCL), Systemic lupus erythematosus (SLE) and Leukodystrophy-related retinopathy (RVCL). Besides, TREX1 inhibits the innate immune response to human immunodeficiency virus type 1 (HIV-1) and plays an important role in mediating the viral immune evasion. Moreover, TREX1 acts as an upstream regulator of the DNA sensing pathway, which maintains tumor immune tolerance and prevents cell senescence. Here, we focus on the immune regulation of TREX1 and demonstrate the role of TREX1 in autoimmune diseases, HIV-1 infection, cancer and cell senescence to provide the basic theoretical guidance for human disease therapy.
张思桐, 杜和康, 陈骐. TREX1介导的免疫调控在疾病中的作用[J]. 中国生物化学与分子生物学报, 2021, 37(11): 1415-1422.
ZHANG Si-Tong, DU He-Kang, CHEN Qi. A Role of TREX1 in Immune Regulation and Human Diseases. Chinese Journal of Biochemistry and Molecular Biol, 2021, 37(11): 1415-1422.
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