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Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia
IL-10 down-regulates the APC function of many dendritic cells (DC),
including human peripheral blood (PB) DC. In rheumatoid arthritis (RA),
synovial fluid (SF) DC express markers of differentiation and are
effective APC despite abundant synovial IL-10. The regulation of DC
responsiveness to IL-10 was therefore examined by comparing the effect
of IL-10 on normal PB and RA SF DC. Whereas IL-10 down-modulated APC
function and MHC class II and B7 expression of PB DC, IL-10 had no such
effect on SF DC. Since SF DC have differentiated in vivo in the
presence of proinflammatory cytokines, PB DC were cocultured in the
presence of IL-10 and either GM-CSF, IL-1ß, TNF-
, IL-6, or
TGF-ß. GM-CSF, IL-1ß, and TNF- were all able to restore APC
function. Whereas the effects of IL-10 on PB DC were shown to be
mediated by IL-10R1, neither PB nor RA SF DC constitutively expressed
IL-10R1 mRNA or detectable surface protein. In contrast, IL-10R1
protein was demonstrated in PB and SF DC whole cell lysates, suggestive
of predominant intracellular localization of the receptor. Thus, DC
responsiveness to IL-10 may be regulated through modulation of cell
surface IL-10R1 expression or signaling.
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