Crucial role for autophagy in degranulation of mast cells

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 FceRI 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/W V 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.