Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation

J Clin Invest. 2003 Mar;111(6):915-24. doi: 10.1172/JCI16156.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Arthritis / etiology*
  • Arthritis / immunology
  • Arthritis / pathology
  • CD11b Antigen / analysis
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Immunohistochemistry
  • Interferon-gamma / physiology
  • Leukocyte Common Antigens / analysis
  • Lymphatic Diseases / etiology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic
  • Repressor Proteins*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • T-Lymphocytes / immunology*


  • CD11b Antigen
  • Carrier Proteins
  • Repressor Proteins
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interferon-gamma
  • Leukocyte Common Antigens