title: Bone marrow chimeric mice reveal a role for CX₃CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium.
abstract: Macrophages in the olfactory neuroepithelium are thought to play major roles in tissue homeostasis and repair. However, little information is available at present about possible heterogeneity of these monocyte-derived cells, their turnover rates, and the role of chemokine receptors in this process. To start addressing these issues, this study used Cx₃cr1(gfp) mice, in which the gene sequence for eGFP was knocked into the CX₃CR1 gene locus in the mutant allele. Using neuroepithelial whole-mounts from Cx₃cr1(gfp/+) mice, we show that eGFP(+) cells of monocytic origin are distributed in a loose network throughout this tissue and can be subdivided further into two immunophenotypically distinct subsets based on MHC-II glycoprotein expression. BM chimeric mice were created using Cx₃cr1(gfp/+) donors to investigate turnover of macrophages (and other monocyte-derived cells) in the olfactory neuroepithelium. Our data indicate that the monocyte-derived cell population in the olfactory neuroepithelium is actively replenished by circulating monocytes and under the experimental conditions, completely turned over within 6 months. Transplantation of Cx₃cr1(gfp/gfp) (i.e., CX₃CR1-deficient) BM partially impaired the replenishment process and resulted in an overall decline of the total monocyte-derived cell number in the olfactory epithelium. Interestingly, replenishment of the CD68(low)MHC-II(+) subset appeared minimally affected by CX₃CR1 deficiency. Taken together, the established baseline data about heterogeneity of monocyte-derived cells, their replenishment rates, and the role of CX₃CR1 provide a solid basis to further examine the importance of different monocyte subsets for neuroregeneration at this unique frontier with the external environment.
authors.affiliation: School of Anatomy and Human Biology, Faculty of Life and Physical Sciences, The University of Western Australia, Crawley, Australia.
authors.forename: Jana
authors.initials: J
authors.lastname: Vukovic
authors.forename: Linda V
authors.initials: LV
authors.lastname: Blomster
authors.forename: Holly R
authors.initials: HR
authors.lastname: Chinnery
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weninger
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Ruitenberg
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D005260:Female; D005455:Fluorescent Antibody Technique; D055879:Gene Knock-In Techniques; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism; D018183:Transplantation Chimera; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000073883:CX3C Chemokine Receptor 1; D000949:Histocompatibility Antigens Class II; D019707:Receptors, Chemokine; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C471885:Cx3cr1 protein, mouse