Cre-Mediated Cell Ablation Contests Mast Cell Contribution in Models of Antibody- and T Cell-Mediated Autoimmunity
2011; Cell Press; Volume: 35; Issue: 5 Linguagem: Inglês
10.1016/j.immuni.2011.09.015
ISSN1097-4180
AutoresThorsten B. Feyerabend, Anne Weiser, Annette Tietz, Michael Stassen, Nicola L. Harris, Manfred Köpf, Peter Radermacher, Peter Möller, Christophe Benoist, Diane Mathis, Hans Jörg Fehling, Hans-Reimer Rodewald,
Tópico(s)Food Allergy and Anaphylaxis Research
ResumoImmunological 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.
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