title: Chemokine receptor CX3CR1 promotes dendritic cell development under steady-state conditions.
abstract: Expression of CX3CR1 is an attribute of myeloid precursors committed to the monocyte/macrophage (Mφ)/DC lineages and is maintained during all stages of DC differentiation. Nevertheless, the exact role of this molecule during developmental progression of myeloid precursors towards the DC lineage remains elusive. To overcome potential compensatory mechanisms and issues of redundancy, we employed competitive adoptive transfer experiments to assess a possible function of CX3CR1 in DC and monocyte/Mφ differentiation in vivo. We show here that expression of CX3CR1 promotes the generation of DCs and monocytes/Mφ under steady-state conditions and during compensatory expansion after selective depletion of DCs, but not under inflammatory conditions evoked by sub-lethal irradiation. Direct administration of CX3CR1-deficient and CX3CR1-sufficient precursors into the spleen or the thymus resulted in a similar competitive advantage of WT over CX3CR1-deficient precursors as i.v. transfer, suggesting that CX3CR1-mediated survival rather than recruitment to lymphoid organs is critical for DC/Mφ differentiation. In conclusion, our data support the hypothesis that CX3CR1 promotes proper development of myeloid precursors into DCs and monocytes/Mφs under steady-state conditions, possibly by providing survival signals or mediating accessibility to organ-specific niches, rather than acting as a mediator of homing to the spleen or the thymus.
authors.affiliation: Institute for Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Łyszkiewicz
authors.forename: Katrin
authors.initials: K
authors.lastname: Witzlau
authors.forename: Jens
authors.initials: J
authors.lastname: Pommerencke
authors.forename: Andreas
authors.initials: A
authors.lastname: Krueger
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055017:Monocyte-Macrophage Precursor Cells / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine