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Mol Immunol. 2014 Jun;59(2):172-9. doi: 10.1016/j.molimm.2014.02.011. Epub 2014 Mar 13.

Serum amyloid A induces mitogenic signals in regulatory T cells via monocyte activation.

Author information

1
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: kdnguyen@stanford.edu.
2
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
3
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: mellins@stanford.edu.

Abstract

Serum amyloid A (SAA) has recently been identified by our group as a mitogen for regulatory T cells (Treg). However, the molecular mechanism by which SAA induces Treg proliferation is unknown. Here we provide evidence that IL-1β and IL-6 are directly involved in the SAA-mediated proliferation of Treg. By engaging its several cognate receptors, SAA induces IL-1β and IL-6 secretion by monocytes and drives them toward an HLA-DR(hi) HVEM(lo) phenotype resembling immature dendritic cells, which have been implicated in tolerance generation. This monocyte-derived cytokine milieu is required for Treg expansion, as inhibition of IL-1β and IL-6 abrogate the ability of SAA to induce Treg proliferation. Furthermore, both IL-1β and IL-6 are required for ERK1/2 and AKT signaling in proliferating Treg. Collectively, these results point to a novel mechanism, by which SAA initiates a monocyte-dependent process that drives mitogenic signals in Treg.

KEYWORDS:

IL-1β; IL-6; Monocytes; Regulatory T cells; Serum amyloid A

PMID:
24632292
PMCID:
PMC4068397
DOI:
10.1016/j.molimm.2014.02.011
[Indexed for MEDLINE]
Free PMC Article

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