Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0509347 on September 16, 2009

Published online before print September 16, 2009
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(Journal of Leukocyte Biology. 2009;86:1359-1363.)
© 2009 Society for Leukocyte Biology

Modulation of human plasmacytoid DC function by IFN-{lambda}1 (IL-29)

Nicholas J. Megjugorac, Grant E. Gallagher and Grant Gallagher1

Genetic Immunology Laboratory, HUMIGEN LLC, the Institute for Genetic Immunology, Hamilton, New Jersey, USA

1. Correspondence: Genetic Immunology Laboratory, HUMIGEN LLC, the Institute for Genetic Immunology, 2439 Kuser Rd., Hamilton, NJ 08690, USA. E-mail: g.gallagher{at}humigen.org

ABSTRACT

The type III family of IFNs displays immunomodulatory and antiviral activity. Each member (IFN-{lambda}1, -2, and -3) signals through the same heterodimeric receptor complex, which consists of the binding and signaling subunit (IL-28R{alpha}) plus the IL-10Rβ chain. Although the receptor has a wide tissue distribution, the direct effects of IFN-{lambda} on various immune cell subsets have not been fully characterized. We have identified high levels of IL-28R{alpha} mRNA in pDC from peripheral blood and hypothesized that IFN-{lambda} plays an important role in pDC maturation and development. We show that stimulation of pDC with HSV or Imiquimod causes an increase in IL-28R{alpha} mRNA. In these cells, IFN-{lambda}1 alters expression of the costimulatory molecules CD80 and ICOS-L and synergizes with IFN-{alpha} to up-regulate CD83. In addition, IFN-{lambda}1 has a variable effect on the homing molecule expression of pDC and mDC. IFN-{lambda}1-treated pDC display a marked difference in their ability to stimulate production of the signature cytokines IL-13, IFN-{gamma}, and IL-10 in a MLR. This work characterizes the variable effects of IFN-{lambda} on DC surface molecule expression and identifies a role in pDC activation and immunostimulatory potential.

Key Words: mDC • ICOS-L • T regulatory cell