[PDF][PDF] Mast cells are crucial for induction of group 2 innate lymphoid cells and clearance of helminth infections

C Shimokawa, T Kanaya, M Hachisuka, K Ishiwata… - Immunity, 2017 - cell.com
C Shimokawa, T Kanaya, M Hachisuka, K Ishiwata, H Hisaeda, Y Kurashima, H Kiyono…
Immunity, 2017cell.com
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 …
Summary
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.
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