6533b7d0fe1ef96bd125b997
RESEARCH PRODUCT
Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.
Peter RadermacherHans Jörg FehlingChristophe BenoistAnne WeiserDiane MathisMichael StassenPeter MöllerAnnette TietzNicola L. HarrisHans Reimer RodewaldThorsten B. FeyerabendManfred Kopfsubject
Cell typeEncephalomyelitis Autoimmune ExperimentalCarboxypeptidases AT cellT-LymphocytesImmunologyAutoimmunityImmunoglobulin E03 medical and health sciencesMice0302 clinical medicineImmune systemTh2 CellsmedicineImmunology and AllergyAnimalsGenetic Predisposition to DiseaseMast CellsIntestinal MucosaInterleukin 5Anaphylaxis030304 developmental biologyAutoantibodiesMice Knockout0303 health sciencesStem Cell FactorbiologyIntegrasesGene Expression ProfilingImmunoglobulin EMast cellArthritis Experimental3. Good healthInterleukin 33Mice Inbred C57BLDisease Models Animalmedicine.anatomical_structureInfectious DiseasesImmunologyGene Targetingbiology.proteinAntibodyTumor Suppressor Protein p53030215 immunologydescription
SummaryImmunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-11-01 | Immunity |