Sökning: onr:"swepub:oai:gup.ub.gu.se/206839" >
S100A4 regulates th...
S100A4 regulates the Src-tyrosine kinase dependent differentiation of Th17 cells in rheumatoid arthritis
-
- Brisslert, Mikael, 1974 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
- Bian, Li, 1966 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
- Svensson, Mattias, 1982 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
visa fler...
-
Santos, R. F. (författare)
-
- Jonsson, Ing-Marie, 1949 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
Barsukov, I. (författare)
-
- Erlandsson, Malin, 1972 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
- Andersson, Karin, 1972 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
Carmo, A. M. (författare)
-
- Bokarewa, Maria, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
visa färre...
-
(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- Engelska.
-
Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1842:11, s. 2049-2059
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Objectives: To evaluate the role of S100A4, a calcium-binding regulator of nonmuscle myosin assembly, for T-cell responses in rheumatoid arthritis. Methods: Arthritis was induced in the methylated bovine serum albumin (mBSA)-immunized mice lacking the entire S100A4 protein (S100A4KO) and in wild-type counterparts treated with short hairpin ribonucleic acid (shRNA)-lentiviral constructs targeting S100A4 (S100A4-shRNA). The severity of arthritis was evaluated morphologically. T-cell subsets were characterized by the expression of master transcription factors, and functionally by proliferation activity and cytokine production. The activity of the Scr-kinases Fyn and Lck was assessed by the autophosphorylation of C-terminal thyrosine and by the phosphorylation of the CD5 cytodomain. The interaction between S100A4 and the CD5 cytodomain was analysed by nuclear magnetic resonance spectrophotometry. Results: S100A4-deficient mice (S100A4KO and S100A4-shRNA) had significantly alleviated morphological signs of arthritis and joint damage. Leukocyte infiltrates in the arthritic joints of S100A4-deficient mice accumulated Foxp3(+) Treg cells, while the number of ROR gamma t(+) and (pTyr705)STAT3(+) cells was reduced. S100A4-deficient mice had a limited formation of Th17-cells with low retinoic acid orphan receptor gamma t (ROR gamma t) mRNA and IL17 production in T-cell cultures. S100A4-deficient mice had a low expression and activity of T-cell receptor (TCR) inhibitor CD5 and low (pTyr705)STAT3 (signal transducer and activator of transcription 3), which led to increased (pTyr352)ZAP-70 (theta-chain associated protein kinase of 70 kDa), lymphocyte proliferation and production of IL2. In vitro experiments showed that S100A4 directly binds Lck and Fyn and reciprocally regulates their kinase activity towards the CD5 cytodomain. Spectrometry demonstrates an interaction between the CD5 cytodomain and EF2-binding sites of S100A4. Conclusion: The present. study demonstrates that S100A4 plays an important part in the pathogenesis of arthritis. It controls CD5-dependent differentiation of Th17 cells by regulating the activity of the Src-family kinases Lck and Fyn. (C) 2014 Elsevier B.V. All rights reserved.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- S100A4
- Th17 cell
- TCR
- Src-tyrosine kinase
- Arthritis
- CD5
- ROR-GAMMA-T
- HUMAN ARTICULAR CHONDROCYTES
- NONMUSCLE MYOSIN-IIA
- GROWTH-FACTOR-BETA
- METASTASIN S100A4
- PROTEIN S100A4
- EFFECTOR
- FUNCTION
- DENDRITIC CELLS
- UP-REGULATION
- FYN KINASE
- Biochemistry & Molecular Biology
- Biophysics
- Cell Biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Brisslert, Mikae ...
-
Bian, Li, 1966
-
Svensson, Mattia ...
-
Santos, R. F.
-
Jonsson, Ing-Mar ...
-
Barsukov, I.
-
visa fler...
-
Erlandsson, Mali ...
-
Andersson, Karin ...
-
Carmo, A. M.
-
Bokarewa, Maria, ...
-
visa färre...
- Om ämnet
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Biologi
-
och Biokemi och mole ...
- Artiklar i publikationen
-
Biochimica Et Bi ...
- Av lärosätet
-
Göteborgs universitet