First Author | Gilchrist M | Year | 2010 |
Journal | Blood | Volume | 115 |
Issue | 23 | Pages | 4734-41 |
PubMed ID | 20203264 | Mgi Jnum | J:161562 |
Mgi Id | MGI:4459613 | Doi | 10.1182/blood-2009-03-213512 |
Citation | Gilchrist M, et al. (2010) A key role for ATF3 in regulating mast cell survival and mediator release. Blood 115(23):4734-41 |
abstractText | Activating transcription factor 3 (ATF3) is a basic leucine zipper transcription factor that plays a regulatory role in inflammation, cell division, and apoptosis. Mast cells (MCs) initiate many inflammatory responses and have a central role in allergy and allergic diseases. We report here that ATF3 has a central role in MC development and function. Bone marrow-derived MC populations from ATF3-deficient mice are unresponsive to interleukin-3 (IL-3)-induced maturation signals, and this correlates with increased apoptosis, diminished activation of the Akt kinase, and decreased phosphorylation of the proapoptotic protein Bad. Furthermore, ATF3-null mice lacked MCs in the peritoneum and dermis, showing that the in vitro results are recapitulated in vivo. ATF3-null MCs also showed functional defects; high-affinity immunoglobulin E receptor-mediated degranulation was significantly inhibited, whereas IL-4 and IL-6 expression was enhanced. This dual role of ATF3 provides insight into the complex interplay between MC development and its subsequent physiologic role. |