CC chemokines

This chapter focuses on CC chemokines, which are a complex system of molecules that affect a variety of hematopoietic and non-hematopoietic cell types. Validation as pharmacological targets includes gene targeting, usage of antibodies or antagonists, whose expression in human pathology is discussed in the chapter. CC chemokine receptor antagonists have been developed, and are at various stages of preclinical or clinical development. CC chemokines are the most numerous, and diversified family of the four subgroups defined, based on the Cys motif (CC, CXC, C, CX3C). In humans, it includes at least 25 members interacting with at least 11 signaling receptors. CC chemokines have been discovered following different pathways, ranging from biological, and biochemical identification to direct cDNA cloning to, more recently, in silico cloning by gene bank mining. The development of efficacious CC chemokine antagonists remains a "holy grail" for the general field of cytokine pharmacology. The chemokines role in the transition from innate to acquired immunity, and in amplification of polarized responses on selected molecules, and pathologies are used as a paradigm.