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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Expression of β-gal reporter gene activity in synovial tissue cells from...
Expression of β-gal reporter gene activity in synovial tissue cells from SOCS-1–/– IFN-γ–/– mice on day 7 of acute arthritis. Synovial tissue cells were isolated by collagenase and dispase digestion of dissected synovium and incubated with FDG for 4 hours. Cells were then stained for expression of phenotypic markers. (a) Cells were stained with CD45 and CD11b, and gated populations were analyzed by light scatter (top row) and β-gal reporter gene activity (bottom row). Cells were incubated in the presence (thin histogram) or absence (bold histogram) of FDG for 4 hours, followed by staining with phenotypic markers. (b) Cytocentrifuge preparations of CD11b+ synovial cells, sorted by flow cytometry on the basis of β-gal activity (Diff-Quik stain; magnification ×400). Results shown are representative of three independent experiments. (c) Lack of reporter gene expression in resident peritoneal macrophages. Resident peritoneal cells from naive SOCS-1–/– IFN-γ–/– mice were stained for CD11b+ expression and β-gal activity. Cells were incubated in the presence (thin histogram) or absence (bold histogram) of FDG for 4 hours. Results shown are gated for CD11b+ cells.