Tsai, Wan-TingWan-TingTsaiLo, Yin-ChiuYin-ChiuLoWu, Ming-SianMing-SianWuLi, Chia-YangChia-YangLiKuo, Yi-PingYi-PingKuoLai, Yi-HuiYi-HuiLaiTsai, YuYuTsaiChen, Kai-ChiehKai-ChiehChenChuang, Tsung-HsienTsung-HsienChuangYao, Chun-HsuChun-HsuYaoLee, Jinq-ChyiJinq-ChyiLeeLI-CHUNG HSUHsu, John T-AJohn T-AHsuYu, Guann-YiGuann-YiYu2019-08-282019-08-28201600219258https://www.scopus.com/inward/record.uri?eid=2-s2.0-84986877476&doi=10.1074%2fjbc.M115.686683&partnerID=40&md5=085209153cb4555ca415279ae7fdc5b7https://scholars.lib.ntu.edu.tw/handle/123456789/416751Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression (e.g. inflammation-associated hepatocellular carcinoma). Immune modulation resulting from pattern recognition receptor-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor- and RIG-I/MAVS-dependent cytokine production through GSH depletion, mitochondrial dysfunction, the activation of p62-associated mitophagy, and p62-TRAF6 interaction. Blockade of autophagy restored the immunosuppressive activity of patulin, and pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases.enRIG-I-like receptor (RLR); immunomodulation; mitochondria; mitophagy; mycotoxin; p62 (sequestosome 1(SQSTM1)); patulin; toll-like receptor (TLR)[SDGs]SDG3Chemical activation; Pathology; Pattern recognition; Adaptive immune response; Cytokine production; Disease progression; Hepatocellular carcinoma; Innate immune response; Mitochondrial dysfunction; Pattern recognition receptors; Toll-like receptors; Immune system; cytokine; glutathione; patulin; protein p62; receptor; retinoic acid inducible protein I; RIG I like receptor; toll like receptor; tumor necrosis factor receptor associated factor 6; unclassified drug; mycotoxin; patulin; sequestosome 1; SQSTM1 protein, human; Sqstm1 protein, mouse; animal cell; animal experiment; Article; autophagy; cell stimulation; controlled study; cytokine production; disease association; disorders of mitochondrial functions; human; human cell; immune deficiency; immunomodulation; immunopathogenesis; inflammation; innate immunity; mitophagy; mouse; nonhuman; priority journal; protein depletion; protein function; protein protein interaction; animal; drug effects; HEK293 cell line; immunology; innate immunity; mitophagy; RAW 264.7 cell line; Animals; HEK293 Cells; Humans; Immunity, Innate; Mice; Mitochondrial Degradation; Mycotoxins; Patulin; RAW 264.7 Cells; Sequestosome-1 Proteinjournal article10.1074/jbc.M115.686683274580132-s2.0-84986877476WOS:000383242800011https://api.elsevier.com/content/abstract/scopus_id/84986877476