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Soluble CD83 inhibits human monocyte differentiation into dendritic cells in vitro
Hongyu Lin1, Shuang Liang2, Zhenyu Zhong3
1Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao 066004, China; Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China; Hebei Engineering and Technology Research Center of Veterinary Biotechnology, Baoding 071001, China.
Insights
Soluble CD83 (sCD83) inhibits human monocyte differentiation into dendritic cells (DCs). This finding suggests a negative feedback mechanism in DC development involving sCD83 released from mature DCs.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD83 is a type I transmembrane glycoprotein primarily found on mature dendritic cells (DCs).
- Both membrane-bound CD83 (mCD83) and soluble CD83 (sCD83) have immunomodulatory roles, with mCD83 being stimulatory and sCD83 inhibitory.
Purpose of the Study:
- To investigate the inhibitory effects of soluble CD83 (sCD83) on human monocyte differentiation into dendritic cells (DCs).
- To explore the potential for sCD83 to act as a negative feedback regulator in DC development.
Main Methods:
- Recombinant human sCD83 was produced in HEK293T cells.
- Human monocytes were cultured in vitro with sCD83 during differentiation into DCs.
- Surface marker expression (CD14, CD1a, CD80, CD86, MHC II) was analyzed to evaluate differentiation.
Main Results:
- Soluble CD83 (sCD83), particularly glycosylated forms, bound to monocytes.
- sCD83 significantly inhibited the downregulation of CD14 expression during differentiation.
- sCD83 reduced the expression of CD1a, CD80, CD86, and MHC II on differentiating cells.
Conclusions:
- Soluble CD83 (sCD83) inhibits the differentiation of human monocytes into dendritic cells (DCs).
- These findings suggest a novel negative feedback loop in DC development mediated by sCD83 released from mature DCs.
Abstract:
Human CD83 is type I transmembrane glycoprotein, mainly expressed on mature dendritic cells (DCs), so it was first described as a molecular marker for mature DC. However, increasing evidence has demonstrated that CD83 is also an immunomodulatory molecule either its membrane-bound CD83 (mCD83) or soluble CD83 (sCD83) released from DCs. Intriguingly, the mCD83 possesses stimulatory effects on immune response, on the contrary, the sCD83 has inhibitory effects. Whether the sCD83 has the inhibitory effects on human monocyte differentiation into DCs is unknown. To this end, we prepared the recombinant human sCD83 in HEK293T cells and treated human monocytes being differentiated into DCs in vitro with the sCD83, and evaluate sCD83 inhibitory effects on immune response by analyzing the surface marker pattern of the cells. The results showed that the sCD83, especially glycosylated sCD83 could bind the monocytes and significantly inhibited the depression of CD14 expressions (P<0.01) and reduced CD1a, CD80, CD86 and MHC II expressions (P<0.01 or P<0.05) during the differentiation, indicating that the sCD83 can inhibit monocyte differentiation into DCs, and suggesting that a negative feedback regulation may exist in monocyte differentiation into DCs based on sCD83 released from the mature DCs.
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