An intricate network of activation and inhibitory signals tightly regulates the cellular responses of various immune cells including eosinophils. To date, multiple activation receptors have been described on eosinophils such as cytokine and chemokine receptors, Fc receptors, and complement receptors. These receptors mediate eosinophil chemotaxis, adhesion, mediator release and survival. In contrast to these activation pathways, an opposing and suppressive receptor system has evolved that has been collectively termed “inhibitory receptors”. The prototype immune inhibitory receptor is identified by a consensus amino acid sequence, the immunoreceptor tyrosine-based inhibitory motif (ITIM), which is present in the cytoplasmic domain of these receptors. Upon receptor:ligand engagement, the ITIM(s) undergo tyrosine phosphorylation and recruit cytoplasmic phosphatases such as the SH2-containing phosphatases-1 (SHP-1) and -2. Inhibitory receptors are thus capable to suppress various cellular responses. Over the last couple of years we focused on the role of the inhibitory receptors paired immunoglobulin-like receptor B (PIR-B), CMRF-like molecule 1 and 8 (also termed CD300lf and CD300a, respectively) in eosinophil migration, survival and mediator release. Basic structure and mechanism of action of these inhibitory receptors will be outlined, as well as a summary of recent advances regarding the roles of such receptors in eosinophils. Finally, the concept of utilizing inhibitory receptors as pharmacological targets for eosinophil suppression will be discussed.
Investigadora de contacte:
Dr. Maria Vicario