Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins

The mounting of an effective immune response requires the coordinated function of both the innate and the adaptive arm of the immune system. Cells from both types of immunity respond to antigenic stimuli through a variety of surface and intracellular receptors and produce cytokines that tightly orch...

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Bibliographic Details
Published in:Immunological reviews 2008-08, Vol.224 (1), p.265-283
Main Authors: Dimitriou, Ioannis D., Clemenza, Liliana, Scotter, Andrew J., Chen, Grace, Guerra, Fiona M., Rottapel, Robert
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - immunology
cytokine signaling
Cytokines - immunology
Cytokines - metabolism
Dendritic Cells - immunology
Dendritic Cells - metabolism
Feedback, Physiological - physiology
Humans
Immune Tolerance
Immunity, Active
Immunity, Innate
Macrophages - immunology
Macrophages - metabolism
Mice
negative regulation
Signal Transduction - immunology
SOCS1
SOCS3
Suppressor of Cytokine Signaling Proteins - chemistry
Suppressor of Cytokine Signaling Proteins - immunology
Suppressor of Cytokine Signaling Proteins - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
TLR signaling
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Summary:The mounting of an effective immune response requires the coordinated function of both the innate and the adaptive arm of the immune system. Cells from both types of immunity respond to antigenic stimuli through a variety of surface and intracellular receptors and produce cytokines that tightly orchestrate the inflammatory response. The operation of feedback control mechanisms that regulate the duration and the amplitude of antigenic and cytokine receptor signaling is therefore required to prevent hyper‐activation of the immune system that could lead to tissue destruction or autoimmunity. Suppressor of cytokine signaling (SOCS) proteins have been identified as a negative feedback loop to cytokine signaling. Recently, the generation of genetically engineered mouse models permitted the evaluation of their function in different processes of the immune responses. In this article, we review new insights into the modular structure of SOCS proteins and the function of SOCS1 and SOCS3 to negatively regulate activation and/or differentiation pathways in macrophages, dendritic cells, and T lymphocytes. Thus, SOCS family proteins are components of an emerging immunoregulatory mechanism that maintains the coordinated balance of both innate and adaptive immune responses.
ISSN:0105-2896
1600-065X
DOI:10.1111/j.1600-065X.2008.00659.x