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lsa.202101067.pdf | 2.68 MB | Adobe PDF | 見る/開く |
タイトル: | TANK prevents IFN-dependent fatal diffuse alveolar hemorrhage by suppressing DNA-cGAS aggregation |
著者: | Wakabayashi, Atsuko Yoshinaga, Masanori Takeuchi, Osamu https://orcid.org/0000-0002-1260-6232 (unconfirmed) |
著者名の別形: | 若林, 敦子 吉永, 正憲 竹内, 理 |
発行日: | Feb-2022 |
出版者: | Life Science Alliance, LLC |
誌名: | Life Science Alliance |
巻: | 5 |
号: | 2 |
論文番号: | e202101067 |
抄録: | Diffuse alveolar hemorrhage (DAH) is one of the serious complications associated with systemic lupus erythematosus, an autoimmune disease whose pathogenesis involves type I IFNs and cytokines. Here, we show that TANK, a negative regulator of the NF-κB signaling via suppression of TRAF6 ubiquitination, is critical for the amelioration of fatal DAH caused by lung vascular endothelial cell death in a mouse model of systemic lupus erythematosus. The development of fatal DAH in the absence of TANK is mediated by type I IFN signaling, but not IL-6. We further uncover that STING, an adaptor essential for the signaling of cytoplasmic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS), plays a critical role in DAH under Tank deficiency. TANK controls cGAS-mediated cGAMP production and suppresses DNA-mediated induction of IFN-stimulated genes in macrophages by inhibiting the formation of DNA-cGAS aggregates containing ubiquitin. Collectively, TANK inhibits the cGAS-dependent recognition of cytoplasmic DNA to prevent fatal DAH in the murine lupus model. |
著作権等: | © 2021 Wakabayashi et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/276721 |
DOI(出版社版): | 10.26508/lsa.202101067 |
PubMed ID: | 34819357 |
出現コレクション: | 学術雑誌掲載論文等 |
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