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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shin, J; Pan, H; Zhong, X-P

Published Date

  • April 2012

Published In

Volume / Issue

  • 119 / 14

Start / End Page

  • 3306 - 3314

PubMed ID

  • 22362037

Pubmed Central ID

  • 22362037

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2011-05-353342

Language

  • eng