title: ICOS ligand expression is essential for allergic airway hyperresponsiveness.
abstract: Inducible co-stimulator ligand (ICOSL) is a rather newly defined co-stimulatory molecule, which, through interaction with ICOS expressed on T cells, plays an important role in T-cell activation, differentiation and function. T(h)2-type immune responses are critical for the development and maintenance of allergic responses including asthma. Using knockout (KO) mice, we have assessed the role of ICOSL in allergic airway inflammation and responsiveness using a standard mouse asthma model induced by ovalbumin (OVA) sensitization and challenge. Our data show that OVA-treated ICOSL KO mice exhibit significantly less lung eosinophilic infiltration, histopathology, mucus production and virtually no airway hyperresponsiveness in contrast to wild-type (Wt) counterparts. Serum antibody analysis showed that antigen-specific IgG1, IgG2a and IgE titers in ICOSL KO mice were significantly lower than those of Wt controls. Also, CD4(+) T cells isolated from ICOSL KO mice produced less T(h)2 cytokines (IL-4, IL-5, IL-10 and IL-13) but more T(h)1 (IFN-γ) and IL-17 than their Wt controls. Taken together, we conclude that ICOSL plays an important role in predisposing individuals to allergic airway hyperresponsiveness by enhancing IgE antibody class switching and T(h)2 cytokine production and diminishing the T(h)17 response and airway eosinophilia.
authors.affiliation: Immune Regulation of Allergy Research Group, Laboratory for Infection and Immunity, Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0W3, Canada.
authors.forename: Kamran
authors.initials: K
authors.lastname: Kadkhoda
authors.forename: Shuhe
authors.initials: S
authors.lastname: Wang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Fan
authors.forename: Hongyu
authors.initials: H
authors.lastname: Qiu
authors.forename: Sujata
authors.initials: S
authors.lastname: Basu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D060945:Inducible T-Cell Co-Stimulator Ligand; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D011506:Proteins; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin