Modulation of human plasmacytoid DC function by IFN-lambda1 (IL-29).
The type III family of IFNs displays immunomodulatory and antiviral activity. Each member (IFN-lambda1, -2, and -3) signals through the same heterodimeric receptor complex, which consists of the binding and signaling subunit (IL-28Ralpha) plus the IL-10Rbeta 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-28Ralpha 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-28Ralpha mRNA. In these cells, IFN-lambda1 alters expression of the costimulatory molecules CD80 and ICOS-L and synergizes with IFN-alpha to up-regulate CD83. In addition, IFN-lambda1 has a variable effect on the homing molecule expression of pDC and mDC. IFN-lambda1-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.
Megjugorac
Nicholas J
NJ
Genetic Immunology Laboratory, HUMIGEN LLC, Institute for Genetic Immunology, Hamilton, New Jersey 08690, USA.
Gallagher
Grant E
GE
Gallagher
Grant
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D000077271:Imiquimod; D007371:Interferon-gamma / Q000276:immunology; D007372:Interferons; D016753:Interleukin-10 / Q000276:immunology; D053710:Interleukin-10 Receptor beta Subunit / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D012333:RNA, Messenger / Q000276:immunology; D018121:Receptors, Cytokine / Q000276:immunology; D000095022:Interferon Lambda
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000077271:Imiquimod; D007371:Interferon-gamma; D007372:Interferons; D016753:Interleukin-10; D053710:Interleukin-10 Receptor beta Subunit; D018793:Interleukin-13; D007378:Interleukins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C508609:IL10 protein, human; C081846:IL10RB protein, human; C471046:interleukin 28alpha receptor