Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation

M. M. Chong, D. Metcalf, E. Jamieson, W. S. Alexander, T. W. Kay

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The balance between pro- and anti-inflammatory cytokines modulates inflammation. Intracellular inhibitors of signaling, in turn, contribute to the negative regulation of cytokines. One of these inhibitors is suppressor of cytokine signaling-1 (SOCS-1). Socs1-/- mice die by 3 weeks of age with inflammation and fatty necrosis of the liver. Here, cre/loxP deletion of Socs1 was used to investigate the contribution of specific cells/tissues to inflammatory disease. Mice with SOCS-1 deficiency in myeloid and lymphoid cells, but not lymphoid alone, became ill at 50 to 250 days of age. These mice developed splenomegaly and T-cell/macrophage infiltration of many organs, including liver, lung, pancreas, and muscle. There were also abnormally high levels of the proinflammatory cytokines interferon γ (IFN-γ), tumor necrosis factor (TNF), and interleukin-12 (IL-12), and activated T cells circulating in these mice. Socs1null T cells were found to be hypersensitive to multiple cytokines, including IL-1, IL-2, and IL-12, resulting in IFN-γ production without requiring T-cell receptor (TCR) ligation. Additionally, Socs1null macrophages produced excessive amounts of IL-12 and TNF in response to other cytokines, including IFN-γ. A dysregulated cytokine network between T cells and macrophages is thus associated with this inflammatory disease. These findings indicate that SOCS-1 is critical in both T cells and macrophages for preventing uncontrolled inflammation.
Original languageEnglish
Pages (from-to)1668-1675
Number of pages9
JournalBlood
Volume106
Issue number5
DOIs
Publication statusPublished - 2005
Externally publishedYes

Fingerprint Dive into the research topics of 'Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation'. Together they form a unique fingerprint.

Cite this