Cigarette smoke-induced accumulation of lung dendritic cells is interleukin-1α-dependent in mice

Respiratory Research

Martin R Stämpfli³  Alison A Humbles¹  Donna Finch²  Roland Kolbeck¹  Yoichiro Iwakura⁴  Mathieu C Morissette⁶  Carla MT Bauer⁵  Jake K Nikota⁵  Fernando M Botelho⁶ 

[1] MedImmune LLC, One MedImmune Way, Gaithersburg, MD, USA;MedImmune LTD, Cambridge, UK;Department of Medicine, McMaster University, Hamilton, Ontario, Canada;Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada;Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Hamilton, Ontario, Canada

关键词: Mice;    CCL20;    T cells;    Dendritic cells;    Cigarette smoke;   

Others  :  796654
DOI  :  10.1186/1465-9921-13-81

 received in 2012-04-25, accepted in 2012-08-29,  发布年份 2012

【 摘 要 】

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.

Conclusion

Our findings convey the importance of IL-1R1/IL-1α to the recruitment and activation of dendritic cells in response to cigarette smoke exposure.

【 授权许可】

   
2012 Botelho et al.; licensee BioMed Central Ltd.

【 图 表 】

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