title: GM-CSF-licensed CD11b+ lung dendritic cells orchestrate Th2 immunity to Blomia tropicalis.
abstract: The Blomia tropicalis dust mite is prevalent in tropical and subtropical regions of the world. Although it is a leading cause of asthma, little is known how it induces allergy. Using a novel murine asthma model induced by intranasal exposure to B. tropicalis, we observed that a single intranasal sensitization to B. tropicalis extract induces strong Th2 priming in the lung draining lymph node. Resident CD11b(+) dendritic cells (DCs) preferentially transport Ag from the lung to the draining lymph node and are crucial for the initiation of Th2 CD4(+) T cell responses. As a consequence, mice selectively deficient in CD11b(+) DCs exhibited attenuated Th2 responses and more importantly did not develop any allergic inflammation. Conversely, mice deficient in CD103(+) DCs and CCR2-dependent monocyte-derived DCs exhibited similar allergic inflammation compared with their wild-type counterparts. We also show that CD11b(+) DCs constitutively express higher levels of GM-CSF receptor compared with CD103(+) DCs and are thus selectively licensed by lung epithelial-derived GM-CSF to induce Th2 immunity. Taken together, our study identifies GM-CSF-licensed CD11b(+) lung DCs as a key component for induction of Th2 responses and represents a potential target for therapeutic intervention in allergy.
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and Singapore Immunology Network, Agency for Science, Technology, and Research, Biopolis, Singapore 138648.
authors.forename: Adrian W S
authors.initials: AW
authors.lastname: Ho
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research, Biopolis, Singapore 138648.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and.
authors.forename: Kenneth H S
authors.initials: KH
authors.lastname: Wong
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and.
authors.forename: Fiona H S
authors.initials: FH
authors.lastname: Wong
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and.
authors.forename: Yen Leong
authors.initials: YL
authors.lastname: Chua
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and.
authors.forename: Veronique
authors.initials: V
authors.lastname: Angeli
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research, Biopolis, Singapore 138648.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology, and Research, Biopolis, Singapore 138648 mickdm@nus.edu.sg Florent_Ginhoux@immunol.a-star.edu.sg.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Immunology Programme, Centre for Life Science, National University of Singapore, Singapore 129793; and mickdm@nus.edu.sg Florent_Ginhoux@immunol.a-star.edu.sg.
authors.forename: David M
authors.initials: DM
authors.lastname: Kemeny
mesh_terms: D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D007114:Immunization / Q000379:methods; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008925:Mites / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014020:Tissue Extracts / Q000008:administration & dosage / Q000276:immunology
chemical_list: D039481:CD11b Antigen; D014020:Tissue Extracts; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin