Inverse Correlation of TRIM32 and Protein Kinase C ζ in T Helper Type 2-Biased Inflammation.
Inverse Correlation of TRIM32 and Protein Kinase C ζ in T Helper Type 2-Biased Inflammation.
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DOI：
10.1016/j.jid.2020.09.021
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Wang Z;Yoo YJ;De La Torre R;Topham C;Hanifin J;Simpson E;Messing RO;Kulesz-Martin M;Liu Y
特应性皮炎(AD)是一种Th2偏向疾病，Th2细胞因子表达升高，对Th2信号阻断有反应。含三方基序的蛋白32(TRIM32)是一种具有天然抗病毒活性的E3泛素连接酶。在我们之前的研究中，我们表明Trim32基因缺失的小鼠在咪喹莫特的反应中出现了偏向Th2的皮肤炎症，并与低水平的TRIM32与AD相关。在本研究中，我们提供了TRIM32缺乏在体外促进Th2细胞分化的证据。对公共数据库中TRIM32相关蛋白的分析表明，PKCζ是一种与TRIM32相关的蛋白，有助于调节Th2信号。我们证明了蛋白激酶Cζ被TRIM32特异性的泛素化，而且在具有TRIM32缺失背景的Th2细胞中，蛋白激酶Cζ的稳定性倾向于增加。此外，Prkcz基因缺失的小鼠在MC903 AD模型中显示出类似AD的受损表型。与健康对照组相比，AD患者皮肤中高PKCζ和低TRIM32值与CD4+细胞有关。综上所述，这些发现表明，TRIM32是蛋白激酶Cζ的调节因子，它控制Th2细胞的分化，这对AD的发病至关重要。
Atopic dermatitis (AD) is a Th2 biased disease with elevated expression of Th2 cytokines that responds to Th2 signaling blockade. Tripartite motif-containing protein 32 (TRIM32) is an E3 ubiquitin ligase with innate antiviral activity. In our previous studies, we showed that Trim32 null mice developed Th2 biased skin inflammation in response to imiquimod and associated low level of TRIM32 with AD. In this study, we provide evidence that TRIM32 deficiency contributes to enhanced Th2 cell differentiation in vitro. Analysis of TRIM32-associated proteins from public databases identified PKCζ as a TRIM32-associated protein that contributes to the regulation of Th2 signaling. We demonstrated that PKCζ was specifically ubiquitinated by TRIM32, and further, that PKCζ stability tended to be increased in Th2 cells with a Trim32 null background. Furthermore, Prkcz null mice showed compromised AD-like phenotypes in the MC903 AD model. Consistently, a high PKCζ and low TRIM32 ratio was associated with CD4+ cells in AD human skin compared with healthy controls. Taken together, these findings suggest that TRIM32 functions as a regulator of PKCζ that controls the differentiation of Th2 cells important for AD pathogenesis.
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影响因子：
5.6
作者：
Rajsbaum, Ricardo;Garcia-Sastre, Adolfo;Versteeg, Gijs A.
通讯作者：
Versteeg, Gijs A.
影响因子：
11.2
作者：
Liu, Yuangang;Lagowski, James;Kulesz-Martin, Molly
通讯作者：
Kulesz-Martin, Molly
特应性皮炎的遗传学和表观遗传学研究
DOI：
10.1186/s13223-016-0158-5
发表时间：
2016
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
Bin L;Leung DY
通讯作者：
Leung DY
影响因子：
6.5
作者：
Chan, SC;Brown, MA;Hanifin, JM
通讯作者：
Hanifin, JM
影响因子：
5.2
作者：
Hillje, Anna-Lena;Worlitzer, Maik M. A.;Schwamborn, Jens C.
通讯作者：
Schwamborn, Jens C.