| First Author | Klein M | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 10 | Pages | 6667-74 |
| PubMed ID | 17082579 | Mgi Jnum | J:140496 |
| Mgi Id | MGI:3813997 | Doi | 10.4049/jimmunol.177.10.6667 |
| Citation | Klein M, et al. (2006) Specific and redundant roles for NFAT transcription factors in the expression of mast cell-derived cytokines. J Immunol 177(10):6667-74 |
| abstractText | By virtue of their ability to express a plethora of biologically highly active mediators, mast cells (MC) are involved in both adaptive and innate immune responses. MC-derived Th2-type cytokines are thought to act as local amplifiers of Th2 reactions, including chronic inflammatory disorders such as allergic asthma, whereas MC-derived TNF-alpha is a critical initiator of antimicrobial defense. In this study, we demonstrate that the transcription factors NFATc1 and NFATc2 are part of a MC-specific signaling network that regulates the expression of TNF-alpha and IL-13, whereas NFATc3 is dispensable. Primary murine bone marrow-derived MC from NFATc2(-/-) mice, activated by either ionomycin or IgE/Ag cross-link, display a strong reduction in the production of these cytokines, compared with bone marrow-derived MC from wild-type mice. Detailed analyses of TNF-alpha and IL-13 expression using small interfering RNA-mediated knockdown reveals that both NFATc2 and NFATc1 are able to drive the expression of these cytokines, whereas neither degranulation nor the expression of IL-6 depends on NFAT activity. These results support the view that high NFAT activity is necessary for TNF-alpha and IL-13 promoter induction in MC, irrespective of whether NFATc2 or NFATc1 or a combination of both is present. |
