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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Tmem176B and Tmem176A are associated with the immature state of dendritic cells
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Tmem176B and Tmem176A are associated with the immature state of dendritic cells

机译：Tmem176B和Tmem176A与树突状细胞的未成熟状态有关

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DCs play a central role in the development of innate and adaptive immunity but also in the induction and maintenance of immune tolerance. Identification of factors that govern DC activation, their maturation state, and their capacity to induce proinflammatory or tolerogeneic responses therefore represents a crucial aim of research. We previously identified a new molecule, Tmem176B (which we named TORID initially), as highly expressed in a model of allograft tolerance in the rat. We showed that its overexpression in rat DCs blocked their maturation, suggesting a role for this molecule in the maturation process. To characterize the function of Tmem176B further, we used a split-ubiquitin yeast, two-hybrid system to identify interacting partners and found that Tmem176B associated with itself but also with Tmem176A, a membrane protein similar to Tmem176B. Interestingly, these two molecules showed similar mRNA expression patterns among various murine tissues and immune cells and were both down-regulated following DC maturation. In addition, we showed that in using RNAi, these molecules are both involved in the maintenance of the immature state of the DCs. Taken together, these data suggest that Tmem176B and Tmem176A associate to form multimers and restrain DC maturation. Therefore, these two molecules may represent valid targets to regulate DC function.
机译：DC在先天和适应性免疫的发展中起着中心作用，在诱导和维持免疫耐受中也起着重要作用。因此，确定决定DC活化的因子，它们的成熟状态及其诱导促炎性或耐受性反应的能力是研究的重要目标。我们先前鉴定了一种新分子Tmem176B（最初将其命名为TORID）在大鼠同种异体移植耐受性模型中高度表达。我们表明其在大鼠DC中的过表达会阻止其成熟，表明该分子在成熟过程中的作用。为了进一步表征Tmem176B的功能，我们使用了分裂泛素酵母双杂交系统来鉴定相互作用的伴侣，并发现Tmem176B不仅与自身相关，而且与Tmem176A（与Tmem176B类似的膜蛋白）相关。有趣的是，这两种分子在各种鼠类组织和免疫细胞中显示出相似的mRNA表达模式，并且在DC成熟后均被下调。此外，我们证明了在使用RNAi时，这些分子都参与了DC的未成熟状态的维持。综上所述，这些数据表明Tmem176B和Tmem176A缔合形成多聚体并抑制DC成熟。因此，这两个分子可能代表调节DC功能的有效目标。

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