Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation
Paul J. Egan, … , Warren S. Alexander, Ian P. Wicks
Paul J. Egan, … , Warren S. Alexander, Ian P. Wicks
Published March 15, 2003
Citation Information: J Clin Invest. 2003;111(6):915-924. https://doi.org/10.1172/JCI16156.
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Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation

Abstract

Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of cytokine signaling. To investigate the role of SOCS-1 in regulating inflammatory and immune responses in disease, acute inflammatory arthritis was induced in mice lacking SOCS-1. Expression of SOCS-1 protein was detected within synovial granulomas and pannus tissue of WT mice by day 7 following induction of acute arthritis. The severity of synovial inflammation and joint destruction at the peak of disease was greater in the absence of SOCS-1, although disease resolution occurred normally. There was an increased percentage of myeloid cells infiltrating the synovium in mice lacking SOCS-1, and SOCS-1 promoter activity was present in synovial macrophages, lymphocytes, and fibroblasts, but not granulocytes. The T cell response in draining LNs was also dysregulated, as popliteal LNs from mice lacking SOCS-1 contained approximately fivefold more cells at the peak of acute arthritis. These cells were hyperproliferative on exposure to antigen in vitro, and purified splenic CD4+ T cells from mice lacking SOCS-1 proliferated more strongly in response to stimulation with anti-CD3. Reporter gene expression was detected in CD4+ T cells bearing the activation markers CD25, CD44, and CD69. SOCS-1 is therefore expressed in hematopoietic and nonhematopoietic cell types in vivo and is an important regulator of acute inflammatory arthritis and of CD4+ T cell activation.

Authors

Paul J. Egan, Kate E. Lawlor, Warren S. Alexander, Ian P. Wicks

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Phenotype of cells accumulating in the synovium of SOCS-1–/– IFN-γ–/– mi...
Phenotype of cells accumulating in the synovium of SOCS-1–/– IFN-γ–/– mice during acute arthritis. Synovium was dissected from the knee joints of SOCS-1+/+ IFN-γ–/– and SOCS-1–/– IFN-γ–/– mice on day 7 after arthritis induction, and synovial cells were isolated by digestion with dispase and collagenase. (a) Increased percentage of myeloid cells in the synovium of SOCS-1–/– IFN-γ–/– mice during acute arthritis. Synovial cells were stained for expression of CD45, and analysis of CD11b and GR-1 expression was performed on CD45+ cells. Results shown are representative of three independent experiments. (b) Flow cytometric analysis of nonadherent synovial cells for expression of CD4 and CD8. Nonadherent synovial cells were isolated following overnight incubation. (c) Cytocentrifuge preparations of joint exudate cells, isolated on day 7 following arthritis induction. ×400.