Abstract
The macrophage stimulating protein (MSP)–Recepteur d’origine nantais (RON) signaling pathway regulates macrophage function. Here, we verified RON receptor expression in bone marrow-derived dendritic cells (BMDCs) by real time-PCR, Western blot, and flow cytometry. Flow cytometry was used to detect the changes in MHC II and CD86 expression following the inhibition of RON in BMDCs and splenic dendritic cells (DCs). Immunoprecipitation and Western blot were used to detect the level of MHC II and CD86 ubiquitination. An enzyme-linked immunosorbent assay was used to detect cytokine release, and a mixed lymphocyte reaction was performed to evaluate DC maturity. The results show that the inhibition of RON leads to an increase in March-1 transcription, which intensifies the ubiquitination of MHC II and CD86 and ultimately leads to a decreased level of these two molecules. The mixed lymphocyte reaction provided evidence that RON inhibition decreased the ability of DCs to promote the proliferation of T cells. The MSP-RON signaling pathway may play an important role in lipopolysaccharide (LPS)-stimulated DC maturation through March-I and may protect DC differentiation following LPS stimulation.
Highlights
Dendritic cells (DCs) represent a type of antigen-presenting cell that recognizes and eliminates invading pathogenic microorganisms through the activation of Toll-like receptors (TLRs)
The level of CD86 and major histocompatibility complex (MHC) II expression was increased in each group stimulated with LPS compared with untreated dendritic cells (DCs)
At the same time, when receiving pathogen-associated molecular pattern stimulation, DCs show increased surface expression of MHC II and CD86, providing the first and costimulatory signals required for T cell activation, resulting in the activation of naive T cells
Summary
Dendritic cells (DCs) represent a type of antigen-presenting cell that recognizes and eliminates invading pathogenic microorganisms through the activation of Toll-like receptors (TLRs). Following DC stimulation with TLR ligands [e.g., lipopolysaccharide (LPS)], immature DCs turn into mature DCs, exhibited by increased major histocompatibility complex (MHC) II and CD86 expression and enhanced release of inflammatory factors. MHC II and CD86 expression in DCs is regulated by ubiquitination and degradation by the E3 ligases March-I and March-8 (Furuta et al, 2013; Oh and Shin, 2015). The expression of March-I in immature DCs enables the cells to recycle MHC II molecules, thereby efficiently treating antigens intracellularly, and loading the antigens onto MHC II. MHC II ubiquitination is MSP-RON Promotes DC Maturation through March-I decreased in LPS-stimulated DCs, which could contribute to maintaining a high level of MHC II expression on the surface of DCs (Cho et al, 2015)
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