title: IL-15 and IL-2 oppositely regulate expression of the chemokine receptor CX3CR1.
abstract: The chemokine receptor CX3CR1 (CX3C chemokine receptor 1) is expressed in mouse blood on natural killer (NK) cells and on monocytes. Because interleukin-15 (IL-15) is an essential cytokine for NK cell development and maintenance, we hypothesized that it may induce CX3CR1 expression on this cell type. In contrast, we found that in primary mouse bone marrow-derived NK cells IL-15 specifically inhibited CX3CR1 protein and mRNA accumulation, whereas the related cytokine IL-2 did not inhibit but instead increased CX3CR1 expression. Consistent with this finding, intravenous injection of a single dose of recombinant IL-15 into C57BL/6 mice decreased steady-state CX3CR1 levels 24 hours after injection in freshly isolated peripheral blood mononuclear cells (PBMCs), splenocytes, and bone marrow cells, and treatment of mouse PBMCs with IL-15 in vitro inhibited CX3CL1 (ligand for CX3CR1)-induced chemotaxis. These data suggest that IL-15 may be a negative regulator of innate immunity by inhibiting CX3CR1 expression. These data also suggest that IL-15 inhibition of CX3CR1 may subvert potential cell immunotherapy strategies in which IL-15 is used to expand NK cell populations in vivo or ex vivo. Finally, our results provide additional evidence for differential signaling by IL-2 and IL-15, despite usage of common beta gamma c receptor chains.
authors.affiliation: molecualr Signalling Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Barlic
authors.forename: Joan M
authors.initials: JM
authors.lastname: Sechler
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002633:Chemotaxis / Q000187:drug effects; D004336:Drug Antagonism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000166:cytology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D012333:RNA, Messenger; D019707:Receptors, Chemokine