Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation
- Author(s)
- Egan, PJ; Lawlor, KE; Alexander, WS; Wicks, IP;
- Details
- Publication Year 2003-03,Volume 111,Issue #6,Page 915-924
- Journal Title
- JOURNAL OF CLINICAL INVESTIGATION
- Publication Type
- Journal Article
- 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.
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Keywords
- COLLAGEN-INDUCED ARTHRITIS; COLONY-STIMULATING FACTOR; RHEUMATOID-ARTHRITIS; JOINT DISEASE; MICE; SOCS-1; INHIBITOR; TNF; INTERLEUKIN-6; INDUCTION
- Publisher's Version
- https://doi.org/10.1172/JCI200316156
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-03-01 12:00:00