Mast cell maturation is driven via a group III phospholipase A 2-prostaglandin D2-DP1 receptor paracrine axis

Yoshitaka Taketomi, Noriko Ueno, Takumi Kojima, Hiroyasu Sato, Remi Murase, Kei Yamamoto, Satoshi Tanaka, Mariko Sakanaka, Masanori Nakamura, Yasumasa Nishito, Momoko Kawana, Naotomo Kambe, Kazutaka Ikeda, Ryo Taguchi, Satoshi Nakamizo, Kenji Kabashima, Michael H. Gelb, Makoto Arita, Takehiko Yokomizo, Motonao NakamuraKikuko Watanabe, Hiroyuki Hirai, Masataka Nakamura, Yoshimichi Okayama, Chisei Ra, Kosuke Aritake, Yoshihiro Urade, Kazushi Morimoto, Yukihiko Sugimoto, Takao Shimizu, Shuh Narumiya, Shuntaro Hara, Makoto Murakami

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast-cell maturation via PGD2 receptor DP1. Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3-null or DP1-null mast cells, or mast cells cultured with L-PGDS-ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation.

Original languageEnglish
Pages (from-to)554-563
Number of pages10
JournalNature Immunology
Volume14
Issue number6
DOIs
Publication statusPublished - Jun 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Taketomi, Y., Ueno, N., Kojima, T., Sato, H., Murase, R., Yamamoto, K., Tanaka, S., Sakanaka, M., Nakamura, M., Nishito, Y., Kawana, M., Kambe, N., Ikeda, K., Taguchi, R., Nakamizo, S., Kabashima, K., Gelb, M. H., Arita, M., Yokomizo, T., ... Murakami, M. (2013). Mast cell maturation is driven via a group III phospholipase A 2-prostaglandin D2-DP1 receptor paracrine axis. Nature Immunology, 14(6), 554-563. https://doi.org/10.1038/ni.2586