title: Cigarette smoke-induced accumulation of lung dendritic cells is interleukin-1α-dependent in mice.
abstract: BACKGROUND
  Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure.
  
  
  METHODS
  Mice were exposed to cigarette smoke using a whole body smoke exposure system. IL-1R1-, TLR4-, and IL-1α-deficient mice, as well as anti-IL-1α and anti-IL-1β blocking antibodies were used to study the importance of IL-1R1 and TLR4 to dendritic cell accumulation and activation.
  
  
  RESULTS
  Acute and chronic cigarette smoke exposure led to increased frequency of lung dendritic cells. Accumulation and activation of dendritic cells was IL-1R1/IL-1α dependent, but TLR4- and IL-1β-independent. Corroborating the cellular data, expression of CCL20, a potent dendritic cells chemoattractant, was IL-1R1/IL-1α-dependent. Studies using IL-1R1 bone marrow-chimeric mice revealed the importance of IL-1R1 signaling on lung structural cells for CCL20 expression. Consistent with the importance of dendritic cells in T cell activation, we observed decreased CD4+ and CD8+ T cell activation in cigarette smoke-exposed IL-1R1-deficient mice.
  
  
  CONCLUSIONS
  Our findings convey the importance of IL-1R1/IL-1α to the recruitment and activation of dendritic cells in response to cigarette smoke exposure.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Hamilton, Ontario, Canada.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Botelho
authors.forename: Jake K
authors.initials: JK
authors.lastname: Nikota
authors.forename: Carla M T
authors.initials: CM
authors.lastname: Bauer
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Morissette
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.forename: Donna
authors.initials: D
authors.lastname: Finch
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D054418:Chemokine CCL20 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D053582:Interleukin-1alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics; D018183:Transplantation Chimera
chemical_list: D019138:Antibodies, Blocking; C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D012906:Smoke; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4