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

Research output: Contribution to journalArticle

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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
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume127
Issue number5
DOIs
Publication statusPublished - May 2011

Fingerprint

Autophagy
Mast Cells
Bone Marrow
Passive Cutaneous Anaphylaxis
Enzyme Induction
Essential Genes
Secretory Vesicles
Starvation
Bone Marrow Cells

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ushio, H., Ueno, T., Kojima, Y., Komatsu, M., Tanaka, S., Yamamoto, A., ... Nakano, H. (2011). Crucial role for autophagy in degranulation of mast cells. Journal of Allergy and Clinical Immunology, 127(5), 1267-1276. https://doi.org/10.1016/j.jaci.2010.12.1078

Crucial role for autophagy in degranulation of mast cells. / Ushio, Hiroko; Ueno, Takashi; Kojima, Yuko; Komatsu, Masaaki; Tanaka, Satoshi; Yamamoto, Akitsugu; Ichimura, Yoshinobu; Ezaki, Junji; Nishida, Keigo; Komazawa-Sakon, Sachiko; Niyonsaba, Franois; Ishii, Tetsuro; Yanagawa, Toru; Kominami, Eiki; Ogawa, Hideoki; Okumura, Ko; Nakano, Hiroyasu.

In: Journal of Allergy and Clinical Immunology, Vol. 127, No. 5, 05.2011, p. 1267-1276.

Research output: Contribution to journalArticle

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, vol. 127, no. 5, pp. 1267-1276. https://doi.org/10.1016/j.jaci.2010.12.1078
Ushio H, Ueno T, Kojima Y, Komatsu M, Tanaka S, Yamamoto A et al. Crucial role for autophagy in degranulation of mast cells. Journal of Allergy and Clinical Immunology. 2011 May;127(5):1267-1276. https://doi.org/10.1016/j.jaci.2010.12.1078
Ushio, Hiroko ; Ueno, Takashi ; Kojima, Yuko ; Komatsu, Masaaki ; Tanaka, Satoshi ; Yamamoto, Akitsugu ; Ichimura, Yoshinobu ; Ezaki, Junji ; Nishida, Keigo ; Komazawa-Sakon, Sachiko ; Niyonsaba, Franois ; Ishii, Tetsuro ; Yanagawa, Toru ; Kominami, Eiki ; Ogawa, Hideoki ; Okumura, Ko ; Nakano, Hiroyasu. / Crucial role for autophagy in degranulation of mast cells. In: Journal of Allergy and Clinical Immunology. 2011 ; Vol. 127, No. 5. pp. 1267-1276.
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AU - Ueno, Takashi

AU - Kojima, Yuko

AU - Komatsu, Masaaki

AU - Tanaka, Satoshi

AU - Yamamoto, Akitsugu

AU - Ichimura, Yoshinobu

AU - Ezaki, Junji

AU - Nishida, Keigo

AU - Komazawa-Sakon, Sachiko

AU - Niyonsaba, Franois

AU - Ishii, Tetsuro

AU - Yanagawa, Toru

AU - Kominami, Eiki

AU - Ogawa, Hideoki

AU - Okumura, Ko

AU - Nakano, Hiroyasu

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