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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Figure 1

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Immunohistochemical staining for SOCS-1 during acute inflammatory arthri...
Immunohistochemical staining for SOCS-1 during acute inflammatory arthritis. Acute inflammatory arthritis was induced by intra-articular injection of 200 μg mBSA into the knee joint followed by three daily subcutaneous injections of 250 ng IL-1β. Mice were sacrificed on day 7 after mBSA injection. Paraffin-embedded joint sections were dewaxed and stained with purified goat polyclonal antibodies specific for SOCS-1 or goat polyclonal antibodies of irrelevant specificity. (a and b) Inflamed WT synovium, stained with antibodies to SOCS-1 (×100, a) or with an isotype control (×100, b). (c) Inflammatory synovial granuloma from a WT mouse, stained with antibodies to SOCS-1 (×400). (d and e) Synovial pannus from a WT mouse, stained with antibodies to SOCS-1 (×400, d) or with an isotype control (×400, e). Arrows in d indicate SOCS-1 positive synovial cells at the cartilage-pannus junction. (f) SOCS-1–/– IFN-γ–/– synovium stained with antibodies to SOCS-1 (×100). (g) Inflamed synovial granuloma from a SOCS-1–/– IFN-γ–/– mouse, stained with antibodies to SOCS-1 (×400).