IL-4-producing ILC2s are required for the differentiation of TH2 cells following Heligmosomoides polygyrus infection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-11

AUTHORS

V S Pelly, Y Kannan, S M Coomes, L J Entwistle, D Rückerl, B Seddon, A S MacDonald, A McKenzie, M S Wilson

ABSTRACT

Immunity to many human and murine gastrointestinal helminth parasites requires interleukin-4 (IL-4)-directed type 2 helper (TH2) differentiation of CD4+ T cells to elicit type-2 immunity. Despite a good understanding of the inflammatory cascade elicited following helminth infection, the initial source of IL-4 is unclear. Previous studies using the rat helminth parasite Nippostronglyus brasiliensis, identified an important role for basophil-derived IL-4 for TH2 differentiation. However, basophils are redundant for TH2 differentiation following infection with the natural helminth parasite of mice Heligmosomoides polygyrus, indicating that other sources of IL-4 are required. In this study using H. polygyrus, which is controlled by IL-4-dependent immunity, we identified that group-2 innate lymphoid cells (ILC2s) produced significant amounts of IL-4 and IL-2 following H. polygyrus infection. Leukotriene D4 was sufficient to stimulate IL-4 secretion by ILC2s, and the supernatant from activated ILC2s could potently drive TH2 differentiation in vitro in an IL-4-dependent manner. Furthermore, specific deletion of IL-4 from ILC2s compromised TH2 differentiation in vivo. Overall, this study highlights a previously unrecognized and important role for ILC2-derived IL-4 for TH2 differentiation in a natural TH2-dependent model of human helminthiasis. More... »

PAGES

1407

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/mi.2016.4

DOI

http://dx.doi.org/10.1038/mi.2016.4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031737667

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26883724


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