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

Journal of Leukocyte Biology

Amelie Lavault²  Maria-Cristina Cuturi²  Frank Halary²  Thomas Condamine²  Laetitia Le Texier²  Marcelo Hill²  Herman Waldmann¹  Steve Cobbold¹  Duncan Howie¹  Elise Chiffoleau² 

[1] Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford University, Oxford, United Kingdom Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford University, Oxford, United Kingdom Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford University, Oxford, United Kingdom;INSERM, U643, CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, and Université de Nantes, Faculté de Médecine, Nantes, France; and INSERM, U643, CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, and Université de Nantes, Faculté de Médecine, Nantes, France; and INSERM, U643, CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, and Université de Nantes, Faculté de Médecine, Nantes, France; and

关键词: cell activation;    antigen presentation;   

DOI  :  10.1189/jlb.1109738

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown