Autoimmunity and Inflammation Due to a Gain-of-Function Mutation in Phospholipase Cγ2 that Specifically Increases External Ca2+ Entry
| Autor: | Ulrike Huffstadt, Matthias Schiemann, Helmut Fuchs, Rainer Constien, Geert C. Mudde, Michael Nehls, Martin Hrabé de Angelis, Andreas Popp, Leticia Quintanilla-Martinez, Sandra Kunder, Philipp Yu, Matilda Katan, Hermann Wagner, Andreas Marquardt, Klaus Pfeffer, Jürgen Laufs, Andreas Russ, Philipp Wabnitz, Andreas Schröder, Christian Schneider-Fresenius, Thomas Peters, Petra Hanke, Kei Yasuda, Neil P. Jones, Michelle Josephs, Johannes Grosse, Neil Dear, Tom D. Bunney, Thomas H. Meyer, Wolfgang Jagla, Carolin Schmittwolf |
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| Jazyk: | angličtina |
| Předmět: |
Male
T cell Molecular Sequence Data Mutant Immunology Autoimmunity Bone Marrow Cells Dermatitis Inflammation Biology medicine.disease_cause Mice Immune system medicine Animals Point Mutation Immunology and Allergy B-Lymphocytes Mutation Base Sequence Phospholipase C gamma Point mutation Autoantibody Arthritis Experimental Up-Regulation medicine.anatomical_structure Infectious Diseases Type C Phospholipases Calcium medicine.symptom |
| Zdroj: | Immunity. (4):451-465 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2005.01.018 |
| Popis: | SummaryThe identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype. |
| Databáze: | OpenAIRE |
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