Type I and III interferons enhance IL-10R expression on human monocytes and macrophages, resulting in IL-10-mediated suppression of TLR-induced IL-12.
Eur J Immunol
; 42(9): 2431-40, 2012 Sep.
Article
in En
| MEDLINE
| ID: mdl-22685028
ABSTRACT
Currently, only about 30-50% of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) patients respond to IFN-based therapy. It has been suggested that IL-10 is involved in suppressing the activity of type I IFNs on antigen-presenting cells (APCs). However, the interaction between type I IFNs and IL-10 is still not clear. Here we report that IFN-α priming upregulated the expression of IL-10R1 on monocytes, and subsequently IL-10 induced a higher level of STAT3 phosphorylation in IFN-primed cells. This indicates that IFN-α increased the sensitivity of monocytes to IL-10, and as a result, TLR-induced IL-12p70 by IFN-pretreated cells was suppressed. Interestingly, both IFN-ß and IL-29, a member of the type III IFN family, comparably sensitized monocytes and macrophages to IL-10 stimulation, indicating a general effect of IFN on the activity of IL-10 in APCs. In summary, we demonstrate that one of the consequences of priming human APCs with IFN is to promote the cells' sensitivity to IL-10, which leads to the inhibition of TLR-induced IL-12p70 production. Therefore, type I and III IFNs induce a suboptimal activation of immune cells. These findings are relevant for the development of strategies to further improve IFN-based therapy for patients with multiple sclerosis or viral hepatitis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Interferon Type I
/
Interleukin-10
/
Interleukin-12
/
Toll-Like Receptors
/
Interleukin-10 Receptor alpha Subunit
/
Macrophages
Limits:
Humans
Language:
En
Journal:
Eur J Immunol
Year:
2012
Document type:
Article
Affiliation country:
Netherlands