IL-27 production and STAT3-dependent upregulation of B7-H1 mediate immune regulatory functions of liver plasmacytoid dendritic cells

Benjamin M. Matta, Giorgio Raimondi, Brian R. Rosborough, Tina L. Sumpter, Angus W. Thomson

Research output: Contribution to journalArticlepeer-review

Abstract

Plasmacytoid dendritic cells (pDCs) are highly specialized APCs that, in addition to their well-recognized role in anti-viral immunity, also regulate immune responses. Liver-resident pDCs are considerably less immunostimulatory than those from secondary lymphoid tissues and are equipped to promote immune tolerance/regulation through various mechanisms. IL-27 is an IL-12 family cytokine that regulates the function of both APCs and T cells, although little is known about its role in pDC immunobiology. In this study, we show that mouse liver pDCs express higher levels of IL-27p28 and EBV-induced protein 3 (Ebi3) compared with those of splenic pDCs. Both populations of pDCs express the IL-27Rα/WSX-1; however, only liver pDCs significantly upregulate expression of the coregulatory molecule B7 homolog-1 (B7-H1) in response to IL-27. Inhibition of STAT3 activation completely abrogates IL- 27-induced upregulation of B7-H1 expression on liver pDCs. Liver pDCs treated with IL-27 increase the percentage of CD4 + Foxp3 + T cells in MLR, which is dependent upon expression of B7-H1. pDCs from Ebi3-deficient mice lacking functional IL-27 show increased capacity to stimulate allogeneic T cell proliferation and IFN-γ production in MLR. Liver but not spleen pDCs suppress delayed-type hypersensitivity responses to OVA, an effect that is lost with Ebi3 -/- and B7-H1 -/- liver pDCs compared with wild-type liver pDCs. These data suggest that IL-27 signaling in pDCs promotes their immunoregulatory function and that IL-27 produced by pDCs contributes to their capacity to regulate immune responses in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)5227-5237
Number of pages11
JournalJournal of Immunology
Volume188
Issue number11
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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