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IL-10 suppresses cell surface CD23/Fc epsilon RII expression, not by enhancing soluble CD23 release, but by reducing
A Morinobu1, S Kumagai, H Yanagida
1Department of Medicine and Clinical Science, Kyoto University, Graduate School of Medicine, Japan.
Insights
Interleukin-10 (IL-10) inhibits interleukin-4 (IL-4)-induced CD23 expression on monocytes at the transcriptional level. This suppression of CD23/Fc epsilon RII on monocytes by IL-10 highlights distinct regulatory pathways compared to B cells.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Interleukin-10 (IL-10) is a cytokine with known immunomodulatory functions.
- CD23, also known as Fc epsilon RII, is a low-affinity receptor for IgE, expressed on various immune cells.
- The regulation of CD23 expression, particularly in monocytes, is complex and involves multiple signaling pathways.
Purpose of the Study:
- To investigate the role of IL-10 in regulating CD23 expression in human monocytes.
- To determine if IL-10 affects surface CD23 expression, soluble CD23 (sCD23) release, or CD23 mRNA levels.
- To compare the effects of IL-10 on CD23 expression in monocytes versus B cells.
Main Methods:
- Human monocytes were cultured and treated with IL-10 and/or IL-4.
- Cell surface CD23 expression was measured using flow cytometry.
- Soluble CD23 (sCD23) levels in culture supernatants were quantified.
- CD23 type b mRNA expression was assessed using RT-PCR.
- Neutralization experiments with anti-IL-10 antibody were performed.
Main Results:
- IL-10 significantly suppressed IL-4-induced surface CD23 expression on monocytes in a dose-dependent manner.
- This suppression was completely blocked by anti-IL-10 antibody.
- IL-10 did not increase the release of sCD23 into the culture supernatant.
- IL-10 markedly reduced IL-4-induced CD23 type b mRNA expression in monocytes.
- While IL-4 induced CD23 on both monocytes and B cells, IL-10's suppressive effect was specific to monocytes.
Conclusions:
- IL-10 inhibits CD23 expression on human monocytes primarily at the transcriptional level.
- The suppressive mechanism of IL-10 on monocyte CD23 expression is not mediated by increased shedding of sCD23.
- Monocytes and B cells exhibit differential regulation of CD23 expression by IL-10, indicating cell-type-specific signaling pathways.
Abstract:
To examine a possible involvement of interleukin-10 (IL-10) in CD23/Fc epsilon RII expression in human monocytes, effects of IL-10 on the cell surface CD23 expression, soluble CD23 (sCD23) release, and CD23 type b mRNA expression were investigated. IL-10 suppressed IL-4-induced surface CD23 expression on monocytes in a dose-dependent manner, and this effect was completely neutralized by anti-IL-10 antibody. The suppressive effect of IL-10 on surface CD23 expression was not due to enhancement of sCD23 release from the cell surface because no increase in sCD23 in culture supernatant was detected after incubation with IL-10. Instead, the effect of IL-10 seemed to be exerted at the transcriptional level since IL-4-induced expression of CD23 type b mRNA was significantly reduced when IL-10 was present. Although IL-4 induced surface CD23 expression on both monocytes and B cells, the suppressive effect of IL-10 was observed only on monocytes, which underscores different regulatory mechanisms for CD23 expression between the two cell types.