Characterisation of Clec12b and its role in immunity and homeostasis

Abstract

C-type lectins are a superfamily of proteins involved in a broad range of functions including the regulation of the immune response and the maintenance of a homeostatic state. Most C-type lectins receptors of the Dectin-1 genomic cluster have been described, and their roles in physiology and pathology have started to be unravelled. However, Clec12b, the last orphan receptor of the Dectin-1 cluster remains poorly characterised. The aim of this work was to describe which cells express Clec12b, and identify potential function(s) and ligand(s) of this receptor. Using a variety of in vitro tools and in vivo experimentations, I showed that murine Clec12b is predominantly expressed in the testis, although its role in the testicular function is unclear. Unlike other members of the Dectin-1 cluster, Clec12b does not seem to be expressed by leukocytes and its contribution toward the regulation of the immune response appears limited. Thanks to newly developed in vitro tools, I demonstrated that Clec12b is not an immune receptor for fungal pathogen Aspergillus fumigatus and that it is not involved in the antifungal immune response against this pathogen. Last, I show that Clec12b possesses an endogenous ligand, whose nature remains unknown. Altogether, this work provides an initial characterisation of Clec12b and its functions, which is likely to constitute a basis for future studies on this receptor.