title: IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke.
abstract: Chronic Obstructive Pulmonary Disease (COPD) is characterized by airspace enlargement and peribronchial lymphoid follicles; however, the immunological mechanisms leading to these pathologic changes remain undefined. Here we show that cigarette smoke is a selective adjuvant that augments in vitro and in vivo Th17, but not Th1, cell differentiation via the aryl hydrocarbon receptor. Smoke exposed IL-17RA(-/-) mice failed to induce CCL2 and MMP12 compared to WT mice. Remarkably, in contrast to WT mice, IL-17RA(-/-) mice failed to develop emphysema after 6 months of cigarette smoke exposure. Taken together, these data demonstrate that cigarette smoke is a potent Th17 adjuvant and that IL-17RA signaling is required for chemokine expression necessary for MMP12 induction and tissue emphysema.
authors.affiliation: Department of Genetics, Louisiana State University Health Science Center, New Orleans, Louisiana, United States of America.
authors.forename: Kong
authors.initials: K
authors.lastname: Chen
authors.forename: Derek A
authors.initials: DA
authors.lastname: Pociask
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: McAleer
authors.forename: Yvonne R
authors.initials: YR
authors.lastname: Chan
authors.forename: John F
authors.initials: JF
authors.lastname: Alcorn
authors.forename: James L
authors.initials: JL
authors.lastname: Kreindler
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Keyser
authors.forename: Steven D
authors.initials: SD
authors.lastname: Shapiro
authors.forename: A McGarry
authors.initials: AM
authors.lastname: Houghton
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Mingquan
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000166:cytology; D018893:Bronchoalveolar Lavage; D002454:Cell Differentiation / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004646:Emphysema / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D012906:Smoke / Q000009:adverse effects*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D014026:Nicotiana / Q000276:immunology*; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018932:Chemokine CCL2; C109985:IL17RA protein, human; D018336:Receptors, Aryl Hydrocarbon; D053722:Receptors, Interleukin-17; D012906:Smoke; D019278:Matrix Metalloproteinase 3; D053508:Matrix Metalloproteinase 12