Lineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis
Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, pla...
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doaj-e78286af00874d5d8ec39239254839ad2020-11-24T23:27:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00555351690Lineage-Specific Analysis of Syk Function in Autoantibody-Induced ArthritisTamás Németh0Tamás Németh1Krisztina Futosi2Krisztina Futosi3Kata Szilveszter4Kata Szilveszter5Olivér Vilinovszki6Levente Kiss-Pápai7Levente Kiss-Pápai8Attila Mócsai9Attila Mócsai10Department of Physiology, Semmelweis University School of Medicine, Budapest, HungaryMTA-SE “Lendület” Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryDepartment of Physiology, Semmelweis University School of Medicine, Budapest, HungaryMTA-SE “Lendület” Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryDepartment of Physiology, Semmelweis University School of Medicine, Budapest, HungaryMTA-SE “Lendület” Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryDepartment of Physiology, Semmelweis University School of Medicine, Budapest, HungaryDepartment of Physiology, Semmelweis University School of Medicine, Budapest, HungaryMTA-SE “Lendület” Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryDepartment of Physiology, Semmelweis University School of Medicine, Budapest, HungaryMTA-SE “Lendület” Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, HungaryAutoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contribute to inflammation and tissue damage in this model. We have previously shown that the Syk tyrosine kinase is critically involved in the development in K/BxN serum-transfer arthritis and bone marrow chimeric experiments indicated that Syk is likely involved in one or more hematopoietic lineages during the disease course. The aim of the present study was to further define the lineage(s) in which Syk expression is required for autoantibody-induced arthritis. To this end, K/BxN serum-transfer arthritis was tested in conditional mutant mice in which Syk was deleted in a lineage-specific manner from neutrophils, platelets, or mast cells. Combination of the MRP8-Cre, PF4-Cre, or Mcpt5-Cre transgene with floxed Syk alleles allowed efficient and selective deletion of Syk from neutrophils, platelets, or mast cells, respectively. This has also been confirmed by defective Syk-dependent in vitro functional responses of the respective cell types. In vivo studies revealed nearly complete defect of the development of K/BxN serum-transfer arthritis upon neutrophil-specific deletion of Syk. By contrast, Syk deletion from platelets or mast cells did not affect the development of K/BxN serum-transfer arthritis. Our results indicate that autoantibody-induced arthritis requires Syk expression in neutrophils, whereas, contrary to prior assumptions, Syk expression in platelets or mast cells is dispensable for disease development in this model.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00555/fullSykarthritisneutrophilsplateletsmast cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tamás Németh Tamás Németh Krisztina Futosi Krisztina Futosi Kata Szilveszter Kata Szilveszter Olivér Vilinovszki Levente Kiss-Pápai Levente Kiss-Pápai Attila Mócsai Attila Mócsai |
spellingShingle |
Tamás Németh Tamás Németh Krisztina Futosi Krisztina Futosi Kata Szilveszter Kata Szilveszter Olivér Vilinovszki Levente Kiss-Pápai Levente Kiss-Pápai Attila Mócsai Attila Mócsai Lineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis Frontiers in Immunology Syk arthritis neutrophils platelets mast cells |
author_facet |
Tamás Németh Tamás Németh Krisztina Futosi Krisztina Futosi Kata Szilveszter Kata Szilveszter Olivér Vilinovszki Levente Kiss-Pápai Levente Kiss-Pápai Attila Mócsai Attila Mócsai |
author_sort |
Tamás Németh |
title |
Lineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis |
title_short |
Lineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis |
title_full |
Lineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis |
title_fullStr |
Lineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis |
title_full_unstemmed |
Lineage-Specific Analysis of Syk Function in Autoantibody-Induced Arthritis |
title_sort |
lineage-specific analysis of syk function in autoantibody-induced arthritis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-03-01 |
description |
Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contribute to inflammation and tissue damage in this model. We have previously shown that the Syk tyrosine kinase is critically involved in the development in K/BxN serum-transfer arthritis and bone marrow chimeric experiments indicated that Syk is likely involved in one or more hematopoietic lineages during the disease course. The aim of the present study was to further define the lineage(s) in which Syk expression is required for autoantibody-induced arthritis. To this end, K/BxN serum-transfer arthritis was tested in conditional mutant mice in which Syk was deleted in a lineage-specific manner from neutrophils, platelets, or mast cells. Combination of the MRP8-Cre, PF4-Cre, or Mcpt5-Cre transgene with floxed Syk alleles allowed efficient and selective deletion of Syk from neutrophils, platelets, or mast cells, respectively. This has also been confirmed by defective Syk-dependent in vitro functional responses of the respective cell types. In vivo studies revealed nearly complete defect of the development of K/BxN serum-transfer arthritis upon neutrophil-specific deletion of Syk. By contrast, Syk deletion from platelets or mast cells did not affect the development of K/BxN serum-transfer arthritis. Our results indicate that autoantibody-induced arthritis requires Syk expression in neutrophils, whereas, contrary to prior assumptions, Syk expression in platelets or mast cells is dispensable for disease development in this model. |
topic |
Syk arthritis neutrophils platelets mast cells |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00555/full |
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