IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice.
Commun Biol
; 4(1): 172, 2021 02 08.
Article
em En
| MEDLINE
| ID: mdl-33558616
ABSTRACT
IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to provide mechanistic insight into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. IL-36 receptor deficient mice exposed to cigarette smoke or cigarette smoke and H1N1 influenza virus had attenuated lung inflammation compared with wild-type controls. We identified neutrophils as a source of IL-36 and show that IL-36 is a key upstream amplifier of lung inflammation by promoting activation of neutrophils, macrophages and fibroblasts through cooperation with GM-CSF and the viral mimic poly(IC). Our data implicate IL-36, independent of other IL-1 family members, as a key upstream amplifier of neutrophilic lung inflammation, providing a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia Viral
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Interleucina-1
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Receptores de Interleucina-1
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Infecções por Orthomyxoviridae
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Ativação de Neutrófilo
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Pulmão
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Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article