Published online before print September 16, 2009
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Article |
1 (IL-29)
Genetic Immunology Laboratory, HUMIGEN LLC, the Institute for Genetic Immunology, Hamilton, New Jersey, USA
@ To whom correspondence should be addressed. E-mail: g.gallagher{at}humigen.org.
The type III family of IFNs displays immunomodulatory and antiviral activity. Each member (IFN-
1, -2, and -3) signals through the same heterodimeric receptor complex, which consists of the binding and signaling subunit (IL-28R
) plus the IL-10R
chain. Although the receptor 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 hypothesized that IFN-
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
mRNA. In these cells, IFN-
1 alters expression of the costimulatory molecules CD80 and ICOS-L and synergizes with IFN-
to up-regulate CD83. In addition, IFN-
1 has a variable effect on the homing molecule expression 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.
Key Words: mDC ICOS-L T regulatory cell