Tmem176B and Tmem176A are associated with the immature state of dendritic cells.
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.
Condamine
Thomas
T
INSERM, U643, CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, and Université de Nantes, Faculté de Médecine, Nantes, France.
Le Texier
Laetitia
L
Howie
Duncan
D
Lavault
Amelie
A
Hill
Marcelo
M
Halary
Frank
F
Cobbold
Steve
S
Waldmann
Herman
H
Cuturi
Maria-Cristina
MC
Chiffoleau
Elise
E
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
D015850:Interleukin-6; D008565:Membrane Proteins; C552365:Tmem176A protein, mouse; C552366:Tmem176B protein, mouse