title: A case of mistaken identity: CD11c-eYFP(+) cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells.
abstract: Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349.
authors.affiliation: Department of Anatomy and Developmental Biology and Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Dando
authors.affiliation: Department of Anatomy and Developmental Biology and Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Naranjo Golborne
authors.affiliation: Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Holly R
authors.initials: HR
authors.lastname: Chinnery
authors.affiliation: School of Biomedical Sciences, the University of Queensland, Brisbane, Queensland, Australia.|Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Ruitenberg
authors.affiliation: Department of Anatomy and Developmental Biology and Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010841:Pia Mater / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D039521:CD11c Antigen; C453730:Crb1 protein, mouse; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; C054562:yellow fluorescent protein, Bacteria; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse
keywords: Crumbs 1; antigen presenting cells; central nervous system; microglia; retinal dystrophic lesions