OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9
OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9
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OTUD1 通过 CARD9 去泛素化调节抗真菌先天免疫
DOI：
10.4049/jimmunol.2001253
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发表时间：
2021-04-15
影响因子：
4.4
通讯作者：
Gao, Chengjiang
中科院分区：
文献类型：
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作者：
Chen, Xiaorong;Zhang, Honghai;Gao, Chengjiang
CARD 9是C型凝集素受体介导的抗真菌天然免疫中的一种必需衔接蛋白。CARD 9的活性受到泛素化的重要调控;然而，参与CARD 9调控的去泛素化酶仍然不完全清楚。在这项研究中，我们确定了卵巢肿瘤去泛素化酶1（OTUD 1）作为CARD 9的重要调节因子。OTUD 1直接与CARD 9相互作用并从CARD 9切割多聚泛素链，导致经典NF-κ B和MAPK途径的激活。OTUD 1缺陷损害CARD 9介导的信号传导，并抑制真菌刺激后的促炎细胞因子产生。重要的是，Otud 1（-/-）小鼠比野生型小鼠更容易受到体内真菌感染。总的来说，我们的研究结果确定OTUD 1作为CARD 9信号通路和抗真菌先天免疫的重要调控组分，通过去泛素化CARD 9。
CARD9 is an essential adaptor protein in antifungal innate immunity mediated by C-type lectin receptors. The activity of CARD9 is critically regulated by ubiquitination; however, the deubiquitinases involved in CARD9 regulation remain incompletely understood. In this study, we identified ovarian tumor deubiquitinase 1 (OTUD1) as an essential regulator of CARD9. OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-kappa B and MAPK pathway. OTUD1 deficiency impaired CARD9-mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation. Importantly, Otud1(-/-) mice were more susceptible to fungal infection than wild-type mice in vivo. Collectively, our results identify OTUD1 as an essential regulatory component for the CARD9 signaling pathway and antifungal innate immunity through deubiquitinating CARD9.