Modulation of human plasmacytoid DC function by IFN-λ1 (IL29

The type III family of IFNs displays immunomodulatory and antiviral activity. Each member (IFN-1,-2, and-3) signals through the same heterodimeric receptor com-plex, which consists of the binding and signaling sub-unit (IL-28R) plus the IL-10R chain. Although the re-ceptor has a wide tissue distribution, the direct effects of IFN- on various immune cell subsets have not been fully characterized. We have identified high levels of IL-28R mRNA in pDC from peripheral blood and hypothe-sized that IFN- plays an important role in pDC matura-tion and development. We show that stimulation of pDC with HSV or Imiquimod causes an increase in IL-28R mRNA. In these cells, IFN-1 alters expression of the costimulatory molecules CD80 and ICOS-L and syner-gizes with IFN- to up-regulate CD83. In addition, IFN-1 has a variable effect on the homing molecule expres-sion of pDC and mDC. IFN-1-treated pDC display a marked difference in their ability to stimulate production of the signature cytokines IL-13, IFN-, and IL-10 in a MLR. This work characterizes the variable effects of IFN- on DC surface molecule expression and identifies a role in pDC activation and immunostimulatory potential. J. Leukoc. Biol. 86: 000–000; 2009