Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity

Thorsten B. Feyerabend, Anne Weiser, Annette Tietz, Michael Stassen, Nicola Harris, Manfred Kopf, Peter Radermacher, Peter Möller, Christophe Benoist, Diane Mathis, Hans Jörg Fehling, Hans Reimer Rodewald

Research output: Contribution to journalArticleResearchpeer-review

237 Citations (Scopus)

Abstract

Immunological 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.

Original languageEnglish
Pages (from-to)832-844
Number of pages13
JournalImmunity
Volume35
Issue number5
DOIs
Publication statusPublished - 23 Nov 2011
Externally publishedYes

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