Regulation of mast cell survival and function by tuberous sclerosis complex 1.

Blood
Jinwook ShinXiao-Ping Zhong

Abstract

Mast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR signaling in mast cells downstream of FcεRI and c-Kit, and differentially controls mast cell degranulation and cytokine production. TSC1-deficiency results in impaired mast cell degranulation, but enhanced cytokine production in vitro and in vivo after FcεRI engagement. Furthermore, TSC1 is critical for mast cell survival through multiple pathways of apoptosis including the down-regulation of p53, miR-34a, reactive oxygen species, and the up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical regulator of mast cell activation and survival, suggesting the manipulation of the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated diseases.

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Citations

Jan 19, 2013·The Journal of Veterinary Medical Science·Yosuke AmagaiHiroshi Matsuda
Mar 13, 2014·The Journal of Clinical Investigation·Jinhong WuXiao-Ping Zhong
Feb 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jinwook ShinXiao-Ping Zhong
Feb 18, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Gerhard J Molderings
Aug 9, 2015·Molecular Immunology·Wei YangJinwook Shin
Oct 16, 2012·European Journal of Immunology·Jinwook ShinXiao-Ping Zhong
Jul 30, 2014·European Journal of Immunology·Riccardo SibilanoCarlo E Pucillo
Sep 26, 2015·Nature Reviews. Immunology·Thomas WeichhartMonika Linke
Nov 25, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenhai DengXiao-Ping Zhong
May 19, 2018·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Bangly SolimanMahmoud El Hefnawi
Aug 29, 2017·Cell Death Discovery·Tarek HazzanMagda Babina
Oct 17, 2014·International Journal of Molecular Medicine·Dong Hwan KimJun Sik Lee
Feb 18, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jinhong WuXiao-Ping Zhong
Jun 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hongjie PanXiao-Ping Zhong
Jul 10, 2018·Immune Network·Valeriya RakhmanovaJinwook Shin
Feb 13, 2021·Molecular and Cellular Biochemistry·Karthik Mallela, Arun Kumar

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