Tmem176B and Tmem176A are associated with the immature state of dendritic cells

Abstract

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, twohybrid 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. J. Leukoc. Biol. 88: 507-515;

Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels

“…These findings suggested that TMEM176A, together with TMEM176B, plays a role in maintaining the immature state of DCs (which seems to no longer be important in more mature DCs). 31 Another study showed that TMEM16A expression levels in the lungs were low, yet proteins levels were increased in patients with lung carcinoma. 43 CHR, Chromosome; FVC, forced vital capacity.…”

“…This suggests that TMEM176A plays a role in the maintenance of the immature state of the DCs. 31 In human subjects Freeman et al found that more severe COPD (according to FEV 1 as percentage predicted) is associated with increased expression of CD40 and CD86 costimulatory molecules on specific types of pulmonary DCs. 46 Nevertheless, the role of DC maturation in patients with (smoking-related) COPD remains controversial, with conflicting data from several in vivo and in vitro studies.…”

“…18,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Several identified SNPs were located in or near genes that might be involved in biological pathway leading to lung function impairment (ie, GALNT13 and PCDH9, respectively). GALNT13 belongs to the GalNAcT family of enzymes, which initiate O-glycosylation of mucins.…”

Identification of Biomarkers for Early Diagnosis of Acute Myocardial Infarction

“…Together with TMEM176B, transmembrane protein 176A has been reported to overexpressed in various cancers Valluri et al, 2012]. Besides, TMEM176A and 176B are also associated with the immature state of dendritic cells [Condamine et al, 2010]. Transcripts of TMEM176A expressed increasingly in liver cancer or kidney tissue; TMEM176B transcripts have significant changes intolerant tissue allografts and tumor cells .…”

Generation and functional characterization of MDSC-like cells

“…Additionally, we found TMEM176A, TMEM176B, SPRY1 as well as MAFB and IRAK3 to be upregulated in IL-10-APC, which are associated with an immature state of DC. For example, the role of TMEM176A and TMEM176B to restrain DC maturation has been demonstrated by expression alteration experiments 14 and SPRY1 has been described to hamper monocyte maturation by interfering with IFN-inducible signaling pathways. 15 Furthermore, we found the transcription factor TFCP2L1 and members of the Kruppel-like transcription factor family to be upregulated in IL-10-APCs, which are also described to play critical roles in monocyte differentiation.…”