Cigarette smoke-induced accumulation of lung dendritic cells is interleukin-1α-dependent in mice
FM Botelho, JK Nikota, CMT Bauer, MC Morissette… - Respiratory …, 2012 - Springer
Respiratory research, 2012•Springer
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 …
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 …
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.
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