The transcription factor CREM drives an inflammatory phenotype of T cells in oligoarticular juvenile idiopathic arthritis

Autor: Patricia Klemm, Dirk Föll, Anja Scheufen, Viktor Wixler, Lucy R. Wedderburn, Halima Moncrieffe, Klaus Tenbrock, Angela Schippers, Norbert Wagner, Helge Nickel, Kim Ohl
Rok vydání: 2018
Předmět:
musculoskeletal diseases
0301 basic medicine
endocrine system
lcsh:Diseases of the musculoskeletal system
T-Lymphocytes
Response element
Cell Culture Techniques
Arthritis
Inflammation
Real-Time Polymerase Chain Reaction
Cyclic AMP Response Element Modulator
03 medical and health sciences
Mice
CREM
Rheumatology
immune system diseases
Synovial joint
Synovial Fluid
medicine
Immunology and Allergy
Animals
Humans
Colitis
Transcription factor
JIA
Effector
business.industry
urogenital system
lcsh:RJ1-570
lcsh:Pediatrics
medicine.disease
Flow Cytometry
Arthritis
Juvenile
030104 developmental biology
medicine.anatomical_structure
Phenotype
Effector T cells
Pediatrics
Perinatology and Child Health
Immunology
Joints
Oligoarticular Juvenile Idiopathic Arthritis
medicine.symptom
lcsh:RC925-935
business
Research Article
Zdroj: Pediatric Rheumatology Online Journal
Pediatric Rheumatology Online Journal, Vol 16, Iss 1, Pp 1-9 (2018)
Pediatric rheumatology 16(1), 39 (2018). doi:10.1186/s12969-018-0253-x
ISSN: 1546-0096
DOI: 10.1186/s12969-018-0253-x
Popis: Background Inflammatory effector T cells trigger inflammation despite increased numbers of Treg cells in the synovial joint of patients suffering from juvenile idiopathic arthritis (JIA). The cAMP response element (CREM)α is known to play a major role in regulation of T cells in SLE, colitis, and EAE. However, its role in regulation of effector T cells within the inflammatory joint is unknown. Methods CREM expression was analyzed in synovial fluid cells from oligoarticular JIA patients by flow cytometry. Peripheral blood mononuclear cells were incubated with synovial fluid and analyzed in the presence and absence of CREM using siRNA experiments for T cell phenotypes. To validate the role of CREM in vivo, ovalbumin-induced T cell dependent arthritis experiments were performed. Results CREM is highly expressed in synovial fluid T cells and its expression can be induced by treating healthy control PBMCs with synovial fluid. Specifically, CREM is more abundant in CD161+ subsets, than CD161− subsets, of T cells and contributes to cytokine expression by these cells. Finally, development of ovalbumin-induced experimental arthritis is ameliorated in mice with adoptively transferred CREM−/− T cells. Conclusion In conclusion, our study reveals that beyond its role in SLE T cells CREM also drives an inflammatory phenotype of T cells in JIA.
Databáze: OpenAIRE
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