D6/ackr2

IN THE BEGINNING . . . Very much in keeping with the name of the chemokine receptor subfamily to which D6 belongs, the majority of my research in the field of chemokine biology has been “atypical” in the sense that it has rarely focused on classical immunological roles for these molecules. Indeed, the story behind the discovery of D6 starts from an unusual research perspective! In 1988, I was employed as a postdoctoral researcher in the laboratory of Prof. Ian Pragnell who became a close friend, and with whom I enjoyed many international adventures. Ian, at the time, was interested in trying to identify inhibitors of hematopoietic stem cell proliferation with the idea that these might be used as myelo protective agents during cancer chemotherapy. He had identified an“activity”in the conditioned media of J774 cells, which was capable of inducing quiescence in primary murine and human hematopoietic stem cells and my job was to purify and characterizes this factor. The protein responsible for this activity proved reasonably easy to purify and turned out to be CCL3 although, at the time, we called it stem cell inhibitor, or SCI. This work was published in Nature in 1990 (1) and represented the first demonstration of a role for chemokines in regulating stem cell function and this, of course, has now become a prominent sub specialty in the chemokine field. The next objective was to clone the receptor for this stem cell inhibitor. I spent a frustrating period of time trying to “expression clone” this CCL3 receptor from “stem cell like” cell lines but these approaches met with little success. Alternative approaches were needed.