title: Th2-type inflammation instructs inflammatory dendritic cells to induce airway hyperreactivity.
abstract: Dendritic cells (DCs) play critical roles in determining the fate of CD4⁺ T cells. Among DC sub-populations, monocyte-derived inflammatory DCs (iDCs) have been shown to play an important role in the induction of adaptive immune responses under inflammatory conditions. Although previous studies have shown that DCs have an indispensable role in the induction of allergic airway inflammation and airway hyperreactivity (AHR) in murine asthma models, the precise roles of iDCs in the asthmatic responses remain largely unknown. We show here that T(h)2 cell-mediated inflammation in murine asthma models induces the expression of some markers of alternatively activated macrophage such as arginase 1 and resistin-like molecule-α in iDCs by a mechanism depending on the intrinsic expression of STAT6. In contrast, T(h)1 cell-mediated inflammation induces iDCs to express TNF-α and inducible nitric oxide synthase (iNOS), markers of TNF-α- and iNOS-producing DCs. Moreover, we show that iDCs under a T(h)2 environment play an important role in the induction of AHR, independently of allergic airway inflammation. Our results thus indicate the importance of iDCs in the induction of AHR as downstream effector cells in T(h)2 cell-mediated asthmatic responses.
authors.affiliation: Department of Allergy and Clinical Immunology and.
authors.forename: Arifumi
authors.initials: A
authors.lastname: Iwata
authors.forename: Saki
authors.initials: S
authors.lastname: Kawashima
authors.forename: Midori
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ayako
authors.initials: A
authors.lastname: Okubo
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kawashima
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirose
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D003170:Complement Pathway, Alternative; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C413576:Retnla protein, mouse; D050800:STAT6 Transcription Factor; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: STAT6; arginase 1; asthma; inflammatory DC