title: Ocular mucosal CD11b+ and CD103+ mouse dendritic cells under normal conditions and in allergic immune responses.
abstract: Steady state dendritic cells (DC) found in non-lymphoid tissue sites under normal physiologic conditions play a pivotal role in triggering T cell responses upon immune provocation. CD11b+ and CD103+ DC have received considerable attention in this regard. However, still unknown is whether such CD11b+ and CD103+ DC even exist in the ocular mucosa, and if so, what functions they have in shaping immune responses. We herein identified in the ocular mucosa of normal wild-type (WT) and Flt3-/- mice the presence of a CD11b+ DC (i.e., CD11c+ MHCII+ CD11b+ CD103- F4/80+ Sirp-a+). CD103+ DC (i.e. CD11c+ MHCII+ CD11b low CD103+ CD8a+ DEC205+ Langerin+) were also present in WT, but not in Flt3-/- mice. These CD103+ DC expressed high levels of Id2 and Flt3 mRNA; whereas CD11b+ DC expressed high Irf4, Csfr, and Cx3cr1 mRNA. Additionally, the functions of these DC differed in response to allergic immune provocation. This was assessed utilizing a previously validated model, which includes transferring specific populations of exogenous DC into the ocular mucosa of ovalbumin (OVA)/alum-primed mice. Interestingly, in such mice, topical OVA instillation following engraftment of exogenous CD11b+ DC led to dominant allergic T cell responses and clinical signs of ocular allergy relative to those engrafted with CD103+ DC. Thus, although CD11b+ and CD103+ DC are both present in the normal ocular mucosa, the CD11b+ DC subset plays a dominant role in a mouse model of ocular allergy.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Khandelwal
authors.forename: Tomas
authors.initials: T
authors.lastname: Blanco-Mezquita
authors.forename: Parisa
authors.initials: P
authors.lastname: Emami
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Lee
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Reyes
authors.forename: Rose
authors.initials: R
authors.lastname: Mathew
authors.forename: Randy
authors.initials: R
authors.lastname: Huang
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005123:Eye / Q000276:immunology*; D005260:Female; D055786:Gene Knockout Techniques; D006967:Hypersensitivity / Q000276:immunology*; D039001:Integrin alpha Chains / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology*; D010641:Phenotype; D014158:Transcription, Genetic; D051941:fms-Like Tyrosine Kinase 3 / Q000172:deficiency / Q000235:genetics
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; C091367:alpha E integrins; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3