RRC ID 48562
Author Shimokawa C, Kanaya T, Hachisuka M, Ishiwata K, Hisaeda H, Kurashima Y, Kiyono H, Yoshimoto T, Kaisho T, Ohno H.
Title Mast Cells Are Crucial for Induction of Group 2 Innate Lymphoid Cells and Clearance of Helminth Infections.
Journal Immunity
Abstract Mast cells are important for eradication of intestinal nematodes; however, their precise mechanisms of action have remained elusive, especially in the early phase of infection. We found that Spi-B-deficient mice had increased numbers of mast cells and rapidly expelled the Heligmosomoides polygyrus (Hp) nematode. This was accompanied by induction of interleukin-13 (IL-13)-producing group 2 innate lymphoid cells (ILC2) and goblet cell hyperplasia. Immediately after Hp infection, mast cells were rapidly activated to produce IL-33 in response to ATP released from apoptotic intestinal epithelial cells. In vivo inhibition of the P2X7 ATP receptor rendered the Spi-B-deficient mice susceptible to Hp, concomitant with elimination of mast cell activation and IL-13-producing ILC2 induction. These results uncover a previously unknown role for mast cells in innate immunity in that activation of mast cells by ATP orchestrates the development of a protective type 2 immune response, in part by producing IL-33, which contributes to ILC2 activation.
Volume 46(5)
Pages 863-874.e4
Published 2017-5-16
DOI 10.1016/j.immuni.2017.04.017
PII S1074-7613(17)30182-6
PMID 28514691
MeSH Adenosine Triphosphate / metabolism Animals Cell Communication Cell Differentiation Disease Models, Animal Disease Resistance / genetics GATA2 Transcription Factor / genetics GATA2 Transcription Factor / metabolism Gene Expression Helminthiasis / genetics Helminthiasis / immunology* Helminthiasis / parasitology* Helminths / immunology* Immunity, Innate* Immunophenotyping Interleukin-33 / metabolism Intestinal Mucosa / immunology Intestinal Mucosa / metabolism Intestinal Mucosa / parasitology Intestinal Mucosa / pathology Lymphocyte Subsets / cytology Lymphocyte Subsets / immunology* Lymphocyte Subsets / metabolism Male Mast Cells / cytology Mast Cells / immunology* Mast Cells / metabolism Mice Mice, Knockout Phenotype Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Receptors, Purinergic P2X7 / metabolism Trans-Activators / genetics Trans-Activators / metabolism Transcription Factors / genetics Transcription Factors / metabolism
IF 22.553
Times Cited 65
DNA material pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).