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IL-31 plays dual roles in lung inflammation in an OVA-induced murine asthma model

Interleukin 31 (IL-31) is a four-helix cytokine made predominantly by Th2 CD4(+) T cells. It was initially identified as being associated with the promotion of atopic dermatitis, where increased levels of IL-31 levels have been found and IL-31 induced the expression of proinflammatory cytokines and...

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Detalles Bibliográficos
Autores principales: Huang, Junqiong, Yue, Huan, Jiang, Tao, Gao, Jing, Shi, Yu, Shi, Bin, Wu, Xiaoxue, Gou, Xiaoqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361213/
https://www.ncbi.nlm.nih.gov/pubmed/30647024
http://dx.doi.org/10.1242/bio.036244
Descripción
Sumario:Interleukin 31 (IL-31) is a four-helix cytokine made predominantly by Th2 CD4(+) T cells. It was initially identified as being associated with the promotion of atopic dermatitis, where increased levels of IL-31 levels have been found and IL-31 induced the expression of proinflammatory cytokines and chemokines in a human bronchial epithelial cell line. However, subsequent study has shown that IL-31RA knockout mice developed exacerbated type 2 inflammation in the lung following infection with Schistosoma mansoni eggs. In this study, we investigated the dynamic expression of IL-31 and IL-31RA during eight consecutive ovalbumin (OVA) challenges and measured the chemokines from lung alveolar epithelial cells induced by IL-31. In addition, we examined the effect deletion of IL-31RA has on lung inflammation and the differentiation of CD4(+) T cells. Our results demonstrate that the expression of IL-31 and IL-31RA was elevated after each weekly OVA challenge, although slightly less of both observed after the first week of OVA challenge. IL-31 also promoted the expression of inflammatory chemokines CCL5, CCL6, CCL11, CCL16, CCL22, CCL28, CX3CL1, CXCL3, CXCL14 and CXCL16 in alveolar epithelial cells. Migration of macrophages and T cells was enhanced by culture supernatants of IL-31-stimulated alveolar epithelial cells. Lastly, and in contrast to the IL-31 results, mice deficient in IL-31RA developed exacerbated lung inflammation, increased IL-4-positive cell infiltrates and elevated Th2 cytokine responses in draining lymph nodes. The proliferation of IL-31RA(−/−) CD4(+) T cells was enhanced in vitro after anti-CD3/anti-CD28 antibody stimulation. These data indicate that IL-31/IL-31RA may play dual roles, first as an early inflammatory mediator promoting the secretion of chemokines to recruit inflammatory cells, and subsequently as a late inflammatory suppressor, limiting Th2 cytokine responses in allergic asthma.