Theranostics 2019; 9(17):4982-4992. doi:10.7150/thno.34001 This issue Cite
Research Paper
1. Department of Gastroenterology, Fifth Hospital, Zhengzhou University, Zhengzhou, China.
2. Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
3. Longgang ENT Hospital & Shenzhen ENT Institute, Shenzhen, China.
4. Department of Respirology, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
5. Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
6. Department of Otolaryngology, First Hospital and Nursing Collage, Shanxi Medical University, Taiyuan, China.
7. State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510006, China.
*Equally contributed to this work
Rationale: Mast cells play a crucial role in allergic diseases. Yet, the regulation of mast cell bioactivities is not fully understood. This study aims to elucidate the role of B cell lymphoma 2 like protein 12 (Bcl2L12), one of the anti-apoptosis proteins, in regulating mast cell apoptosis.
Methods: A food allergy (FA) mouse model was developed to establish mast cell over population in the intestinal tissue. Either compound 48/80 (C48/80) or specific antigens were used to activate mast cells in the intestinal mucosa.
Results: After treating with C48/80, apoptosis was induced in mast cells of the intestine of naive control mice, but not in FA mice. The expression of Fas ligand (FasL) was lower in the mast cells of FA mice. Interleukin (IL)-5 was responsible for the suppression of FasL by upregulating the expression of Bcl2L12 in mast cells. Bcl2L12 prevented c-Myc, the major transcription factor of FasL, from binding the FasL promoter to inhibit the expression of FasL in mast cells. Inhibition of Bcl2L12 restored the apoptosis machinery of mast cells in the FA mouse intestine.
Conclusions: The apoptosis machinery in mast cells is impaired in an allergic environment. Inhibition of Bcl2L12 restores the apoptosis machinery in mast cells in the FA mouse intestine.
Keywords: Mast cell, inflammation, immunology, apoptosis, interleukin-5.