title: Multiple chemokine receptors, including CCR6 and CXCR3, regulate antigen-induced T cell homing to the human asthmatic airway.
abstract: Human allergic asthma is a chronic inflammatory disease of the airways thought to be driven by allergen-specific Th2 cells, which are recruited into the lung in response to inhaled allergen. To identify chemoattractant receptors that control this homing pattern, we used endobronchial segmental allergen challenge in human atopic asthmatics to define the pattern of chemoattractant receptor expression on recruited T cells as well as the numbers of recruited CD1d-restricted NKT cells and levels of chemokines in the bronchoalveolar (BAL) fluid. CD1d-restricted NKT cells comprised only a small minority of BAL T cells before or after Ag challenge. BAL T cells were enriched in their expression of specific chemoattractant receptors compared with peripheral blood T cells prechallenge, including CCR5, CCR6, CXCR3, CXCR4, and BLT1. Surprisingly, following segmental allergen challenge, no chemoattractant receptor was specifically increased. However, CCR6 and CXCR3, which were expressed on virtually all CD4(+) BAL T cells prechallenge, were markedly decreased on all recruited BAL T cells following Ag challenge, suggesting that these receptors were internalized following encounter with ligand in the airway. Our data therefore suggests a role for CCR6 and CXCR3, in conjunction with other chemoattractant receptors, in the recruitment of inflammatory T cells into the BAL during the allergic asthmatic response.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Seddon Y
authors.initials: SY
authors.lastname: Thomas
authors.forename: Aleena
authors.initials: A
authors.lastname: Banerji
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Craig M
authors.initials: CM
authors.lastname: Lilly
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000485:Allergens; C106311:CCR6 protein, human; C515187:CXCR3 protein, human; D018984:Epitopes, T-Lymphocyte; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma