CCR5 attenuates neutrophilic airway inflammation exacerbated by infection with rhinovirus

•CCR5 attenuates neutrophilic airway inflammation in hRV-induced asthma exacerbation.•CCR5 ablation results in enhanced influx of Siglec-F+Gr-1+ neutrophils by IL-17A and IFN-γ production in inflamed tissues.•But, CCR5 ablation down-regulates Th2-related cytokine production following hRV infection.•...

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Published in:Cellular immunology 2020-05, Vol.351, p.104066-104066, Article 104066
Main Authors: Hossain, Ferdaus Mohd Altaf, Park, Seong Ok, Kim, Hyo Jin, Eo, Jun Cheol, Choi, Jin Young, Uyangaa, Erdenebelig, Kim, Bumseok, Kim, Koanhoi, Eo, Seong Kug
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Language:English
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Summary:•CCR5 attenuates neutrophilic airway inflammation in hRV-induced asthma exacerbation.•CCR5 ablation results in enhanced influx of Siglec-F+Gr-1+ neutrophils by IL-17A and IFN-γ production in inflamed tissues.•But, CCR5 ablation down-regulates Th2-related cytokine production following hRV infection.•CCR5 ablation alters the equilibrium of CD4+FoxP3+ Tregs and IL-17+CD4+ Th17 in inflamed tissues. Human rhinovirus (hRV) is the most common cause of asthma exacerbation characterized by clinical and pathophysiological heterogeneity. Steroid-sensitive, Th2 type-eosinophilic asthma has been somewhat studied, but hRV-induced neutrophilic asthma exacerbation is poorly understood. Here, CCR5 was found to play a role in attenuating neutrophilic airway inflammation in hRV-induced asthma exacerbation using chicken ovalbumin (OVA)-based model. CCR5 deficiency resulted in exacerbated neutrophilic asthmatic responses in airways following hRV infection. CCR5-deficient mice showed enhanced mucus expression and altered expression of tight junction proteins in lung tissues. CCR5-deficient mice were also manifested with influx of CD45+CD11b+Siglec-F+Gr-1+ neutrophils, along with enhanced production of IL-17A, IFN-γ, IL-6, IL-1β cytokines in inflamed tissues. In contrast, CCR5-deficient mice elicited down-regulation of Th2-related cytokine proteins following hRV infection. More interestingly, the lack of CCR5 altered the equilibrium of CD4+FoxP3+ Tregs and IL-17+CD4+ Th17 in inflamed tissues. CCR5-deficient mice showed increased frequency and absolute number of IL-17-producing CD4+ Th17 cells in lung tissues compared to wild-type mice, whereas the reduced infiltration of CD4+FoxP3+ Treg cells was observed. CCR5 deficiency resulted in the skewed production of Th17 and Th1 cytokines in lymph nodes and lungs upon OVA stimulation. Likewise, CCR5-deficient mice showed enhanced expression of Th17-inducing cytokines (IL-1β, IL-6, and TNF-α) in lung tissues. These results imply that CCR5 deficiency facilitates Th17 airway inflammation during hRV-induced asthma exacerbation, along with suppressing Th2 responses. Furthermore, our results suggest that CCR5 attenuates hRV-induced neutrophilic airway inflammation through conserving the equilibrium of CD4+Foxp3+ Treg cells and IL-17+CD4+ Th17 cells in hRV-induced asthma exacerbation.
ISSN:0008-8749
1090-2163
DOI:10.1016/j.cellimm.2020.104066