Lineage-specific analysis of Syk function in autoantibody-induced arthritis

T. Németh, Krisztina Futosi, Kata Szilveszter, Olivér Vilinovszki, Levente Kiss-Pápai, A. Mócsai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number555
JournalFrontiers in Immunology
Volume9
Issue numberMAR
DOIs
Publication statusPublished - Mar 19 2018

Fingerprint

Autoantibodies
Arthritis
Mast Cells
Neutrophils
Blood Platelets
Serum
Inflammation
Transgenes
Protein-Tyrosine Kinases
Autoimmune Diseases
Bone Marrow
Alleles
Pathology

Keywords

  • Arthritis
  • Mast cells
  • Neutrophils
  • Platelets
  • Syk

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lineage-specific analysis of Syk function in autoantibody-induced arthritis. / Németh, T.; Futosi, Krisztina; Szilveszter, Kata; Vilinovszki, Olivér; Kiss-Pápai, Levente; Mócsai, A.

In: Frontiers in Immunology, Vol. 9, No. MAR, 555, 19.03.2018.

Research output: Contribution to journalArticle

Németh, T. ; Futosi, Krisztina ; Szilveszter, Kata ; Vilinovszki, Olivér ; Kiss-Pápai, Levente ; Mócsai, A. / Lineage-specific analysis of Syk function in autoantibody-induced arthritis. In: Frontiers in Immunology. 2018 ; Vol. 9, No. MAR.
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