Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation.
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.
Egan
Paul J
PJ
Reid Rheumatology Laboratory, Division of Autoimmunity and Transplantation, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Lawlor
Kate E
KE
Alexander
Warren S
WS
Wicks
Ian P
IP
D000208:Acute Disease; D000818:Animals; D001168:Arthritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D039481:CD11b Antigen / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000032:analysis; D008206:Lymphatic Diseases / Q000209:etiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D039481:CD11b Antigen; D002352:Carrier Proteins; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens