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Modulation of human plasmacytoid DC function by IFN‐λ1 (IL‐29)

The type III family of IFNs displays immunomodulatory and antiviral activity. Each member (IFN‐λ1, −2, and −3) signals through the same heterodimeric receptor complex, which consists of the binding and signaling subunit (IL‐28Rα) plus the IL‐10Rβ chain. Although the receptor has a wide tissue distribution, the direct effects of IFN‐λ on various immune cell subsets have not been fully characterized. We have identified high levels of IL‐28Rα mRNA in pDC from peripheral blood and hypothesized that IFN‐λ plays an important role in pDC maturation and development. We show that stimulation of pDC with HSV or Imiquimod causes an increase in IL‐28Rα mRNA. In these cells, IFN‐λ1 alters expression of the costimulatory molecules CD80 and ICOS‐L and synergizes with IFN‐α to up‐regulate CD83. In addition, IFN‐λ1 has a variable effect on the homing molecule expression of pDC and mDC. IFN‐λ1‐treated pDC display a marked difference in their ability to stimulate production of the signature cytokines IL‐13, IFN‐γ, and IL‐10 in a MLR. This work characterizes the variable effects of IFN‐λ on DC surface molecule expression and identifies a role in pDC activation and immunostimulatory potential.