Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by human dendritic cells
Beaulieu,Sylvie; Robbiani,Davide F.; Du,Xixuan; Rodrigues,Elaine; Ignatius,Ralf; Wei,Yang; Ponath,Paul; Young,James W.; Pope,Melissa; Steinman,Ralph M.; Mojsov,Svetlana
Journal of Immunology 169(6): 2925-2936
Publication date: 2002
Critical to the function of Ag-presenting dendritic cells (DCs)is their capacity to migrate to lymphoid organs and to sitesof inflammation. A final stage of development, termed maturation,yields DCs that are strong stimulators of T cell-mediated immunityand is associated with a remodeling of the cell surface thatincludes a change in the levels of expression of many molecules,including chemokine receptors. We show in this study that CCR3,a chemokine receptor initially discovered on eosinophils, isalso expressed by human DCs that differentiate from blood monocytes,DCs that emigrate from skin (epidermal and dermal DCs), andDCs derived from CD34 hemopoietic precursors in bone marrow,umbilical cord blood, and cytokine-elicited peripheral bloodleukapheresis. Unlike other chemokine receptors, such as CCR5and CCR7, the expression of CCR3 is not dependent on the stateof maturation. All DC subsets contain a large intracellularpool of CCR3. The surface expression of CCR3 is not modulatedfollowing uptake of particulate substances such as zymosan or latexbeads. CCR3 mediates in vitro chemotactic responses to the knownligands, eotaxin and eotaxin-2, because the DC response to these chemokinesis inhibited by CCR3-specific mAbs. We postulate that expressionof CCR3 may underlie situations where both DCs and eosinophilsaccumulate in vivo, such as the lesions of patients with Langerhanscell granulomatosis.