Crucial role for autophagy in degranulation of mast cells

Hiroko Ushio, Takashi Ueno, Yuko Kojima, Masaaki Komatsu, Satoshi Tanaka, Akitsugu Yamamoto, Yoshinobu Ichimura, Junji Ezaki, Keigo Nishida, Sachiko Komazawa-Sakon, Franois Niyonsaba, Tetsuro Ishii, Toru Yanagawa, Eiki Kominami, Hideoki Ogawa, Ko Okumura, Hiroyasu Nakano

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77 Citations (Scopus)

Abstract

Background: Autophagy plays a crucial role in controlling various biological responses including starvation, homeostatic turnover of long-lived proteins, and invasion of bacteria. However, a role for autophagy in development and/or function of mast cells is unknown. Objective: To investigate a role for autophagy in mast cells, we generated bone marrow-derived mast cells (BMMCs) from mice lacking autophagy related gene (Atg) 7, an essential enzyme for autophagy induction. Methods: Bone marrow-derived mast cells were generated from bone marrow cells of control and IFN-inducible Atg7-deficient mice, and morphologic and functional analyses were performed. Results: We found that conversion of type I to type II light chain (LC3)-II, a hallmark of autophagy, was constitutively induced in mast cells under full nutrient conditions, and LC3-II localized in secretory granules of mast cells. Although deletion of Atg7 did not impair the development of BMMCs, Atg7-/- BMMCs showed severe impairment of degranulation, but not cytokine production on FcεRI cross-linking. Intriguingly, LC3-II but not LC3-I was co-localized with CD63, a secretory lysosomal marker, and was released extracellularly along with degranulation in Atg7+/+ but not Atg7-/- BMMCs. Moreover, passive cutaneous anaphylaxis reactions were severely impaired in mast cell-deficient WBB6F1-W/WV mice reconstituted with Atg7-/- BMMCs compared with Atg7+/+ BMMCs. Conclusion: These results suggest that autophagy is not essential for the development but plays a crucial role in degranulation of mast cells. Thus, autophagy might be a potential target to treat allergic diseases in which mast cells are critically involved.

Original languageEnglish
Pages (from-to)1267-1276.e6
JournalJournal of Allergy and Clinical Immunology
Volume127
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • CD63
  • Mast cell
  • autophagy
  • degranulation
  • light chain 3 (LC3)
  • p62

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ushio, H., Ueno, T., Kojima, Y., Komatsu, M., Tanaka, S., Yamamoto, A., Ichimura, Y., Ezaki, J., Nishida, K., Komazawa-Sakon, S., Niyonsaba, F., Ishii, T., Yanagawa, T., Kominami, E., Ogawa, H., Okumura, K., & Nakano, H. (2011). Crucial role for autophagy in degranulation of mast cells. Journal of Allergy and Clinical Immunology, 127(5), 1267-1276.e6. https://doi.org/10.1016/j.jaci.2010.12.1078