IL-10 production by ILC2s requires Blimp-1 and cMaf, modulates cellular metabolism, and ameliorates airway hyperreactivity.
J Allergy Clin Immunol
; 147(4): 1281-1295.e5, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-32905799
ABSTRACT
BACKGROUND:
Group 2 innate lymphoid cells (ILC2s) are the dominant innate lymphoid cell population in the lungs at steady state, and their release of type 2 cytokines is a central driver in responding eosinophil infiltration and increased airway hyperreactivity. Our laboratory has identified a unique subset of ILC2s in the lungs that actively produce IL-10 (ILC210s).OBJECTIVE:
Our aim was to characterize the effector functions of ILC210s in the development and pathology of allergic asthma.METHODS:
IL-4-stimulated ILC210s were isolated to evaluate cytokine secretion, transcription factor signaling, metabolic dependence, and effector functions in vitro. ILC210s were also adoptively transferred into Rag2-/-γc-/- mice, which were then challenged with IL-33 and assessed for airway hyperreactivity and lung inflammation.RESULTS:
We have determined that the transcription factors cMaf and Blimp-1 regulate IL-10 expression in ILC210s. Strikingly, our results demonstrate that ILC210s can utilize both autocrine and paracrine signaling to suppress proinflammatory ILC2 effector functions in vitro. Further, this subset dampens airway hyperreactivity and significantly reduces lung inflammation in vivo. Interestingly, ILC210s demonstrated a metabolic dependency on the glycolytic pathway for IL-10 production, shifting from the fatty acid oxidation pathway conventionally utilized for proinflammatory effector functions.CONCLUSION:
These findings provide an important and previously unrecognized role of ILC210s in diseases associated with ILC2s such as allergic lung inflammation and asthma. They also provide new insights into the metabolism dependency of proinflammatory and anti-inflammatory ILC2 phenotypes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Linfócitos
/
Interleucina-10
/
Hiper-Reatividade Brônquica
/
Proteínas Proto-Oncogênicas c-maf
/
Fator 1 de Ligação ao Domínio I Regulador Positivo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2021
Tipo de documento:
Article