Abstract
The acute phase protein serum amyloid A (SAA) has been well characterized as an indicator of inflammation. Nevertheless, its functions in pro versus anti-inflammatory processes remain obscure. Here we provide unexpected evidences that SAA induces the proliferation of the tolerogenic subset of regulatory T cells (T(reg)). Intriguingly, SAA reverses T(reg) anergy via its interaction with monocytes to activate distinct mitogenic pathways in T(reg) but not effector T cells. This selective responsiveness of T(reg) correlates with their diminished expression of SOCS3 and is antagonized by T(reg)-specific induction of this regulator of cytokine signaling. Collectively, these evidences suggest a novel anti-inflammatory role of SAA in the induction of a micro-environment that supports T(reg) expansion at sites of infection or tissue injury, likely to curb (auto)-inflammatory responses.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Communication / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Child
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Clonal Anergy / drug effects*
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Humans
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Inflammation / immunology
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Inflammation / metabolism
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Inflammation / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Monocytes / drug effects
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Monocytes / immunology
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Monocytes / metabolism
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Monocytes / physiology*
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Serum Amyloid A Protein / pharmacology*
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Serum Amyloid A Protein / physiology
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins / antagonists & inhibitors*
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Suppressor of Cytokine Signaling Proteins / metabolism
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Suppressor of Cytokine Signaling Proteins / physiology
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T-Lymphocytes, Regulatory / drug effects*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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T-Lymphocytes, Regulatory / physiology
Substances
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Serum Amyloid A Protein
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Socs3 protein, mouse
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins