6533b82efe1ef96bd1292873
RESEARCH PRODUCT
Specific and Redundant Roles for NFAT Transcription Factors in the Expression of Mast Cell-Derived Cytokines
Marc BeckerMichael StassenStefan Klein-hesslingEdgar SchmittChristine TertiltValeska HeibEdgar SerflingTobias BoppHansjörg SchildMatthias KleinChristian TaubeAlois Palmetshofersubject
ImmunologyDown-RegulationImmunoglobulin EMicechemistry.chemical_compoundTh2 CellsCell Line TumormedicineAnimalsImmunology and AllergyMast CellsTranscription factorCells CulturedMice KnockoutMice Inbred BALB CGene knockdownInterleukin-13Innate immune systemNFATC Transcription FactorsbiologyTumor Necrosis Factor-alphaDegranulationNFATMast cellUp-RegulationCell biologymedicine.anatomical_structurechemistryIonomycinImmunologybiology.proteinCytokinesdescription
Abstract 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-α 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-α 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-α 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-α and IL-13 promoter induction in MC, irrespective of whether NFATc2 or NFATc1 or a combination of both is present.
year | journal | country | edition | language |
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2006-11-04 | The Journal of Immunology |