Reference - Detail
|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.|
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.
|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|
|DNA material||pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).|