Receptors controlling the innate immune system

Myeloid cells are activated quickly at the start of an immune response and play a central role in the orchestration of the secondary, adaptive immune response. The adaptive response is influenced both indirectly, through the secretion of cytokines that re gulate the type of immune response generated, and directly through presentation of antigens to T cells. The control of myeloid cells is thus crucial to the outcome of the immune response. We recently identified a novel family of receptors, the CD300 famil y, which comprises receptors with both activating and inhibitory type signalling domains, indicating that CD300 receptors have the potential to control activation of the myeloid response as well as to limit its extent. This may be particular pertinent to the linkage of the CD300 complex to autoimmune and atopic diseases. The main goals of the study are to increase our knowledge of the CD300 receptor family, and to examine the role that these receptors play in myeloid cell function. The studies will be fo cussed in the following areas: a. Expression of CD300 receptors: We will examine expression of CD300 receptors on myeloid cells and look to see how this expression is affected by a variety of stimuli. We will also examine CD300 expression in rheumatoid a rthritis using realtime PCR. b. Signal transduction studies: We will examine the signalling machinery employed by selected CD300 receptors, and relate this to function. c. Ligand identification: Novel methods will be employed for identification of CD300 ligands. We have used these techniques to identify the ligands for similar receptors and believe that we are well equipped for success in this area. d. Functional studies: Prior to ligand identification, studies will be initiated using antibodies for st imulation or blocking of receptor function. We will also use RNAi technology to block CD300 expression. Function will be analysed with a combination of in vitro and in vivo assays.