FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells
Journal
Frontiers in immunology
Journal Volume
8
Journal Issue
OCT
Date Issued
2017
Author(s)
Abstract
The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FcεRI γ-chain (FcRγ) has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs). Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes. In addition, increments of T cell activation and T helper 17 polarization induced by FcRγ-deficient DCs were observed both in vitro and in vivo. Examining the Dectin-1 signaling, we revealed that the activations of several signaling molecules were augmented in FcRγ-deficient DCs stimulated with Dectin-1 ligands. Furthermore, we demonstrated that the association of phosphatases SHP-1 and PTEN with FcRγ may contribute to the negative regulation of FcRγ in Dectin-1 activation in DCs. These results extend the inhibitory effect of ITAM-containing adapters to Dectin-1 response in immune functions, even though Dectin-1 contains an ITAM-like intracellular domain. According to the role of Dectin-1 in responding to microbes and tumor cells, our finding may have applications in the development of vaccine and cancer therapy.
Subjects
DAP12; Dectin-1; FcεRI γ-chain; PTEN; SHP-1; dendritic cell; immunoreceptor tyrosine-based activation motif
SDGs
Other Subjects
B7 antigen; CD40 antigen; CD86 antigen; chemokine receptor CCR7; dectin 1; dectin 2; glyceraldehyde 3 phosphate dehydrogenase; glycoprotein p 15095; immunoglobulin E receptor; interleukin 10; interleukin 2; interleukin 23; interleukin 6; major histocompatibility antigen class 2; mitogen activated protein kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; phosphatidylinositol 4,5 bisphosphate phosphodiesterase; protein kinase B; protein kinase Syk; protein tyrosine kinase; protein tyrosine phosphatase SHP 1; Raf protein; animal cell; antigen specificity; Article; cell maturation; cell migration; cellular immunity; controlled study; cytokine production; dendritic cell; enzyme linked immunosorbent assay; flow cytometry; immunomodulation; immunoprecipitation; immunoreceptor tyrosine based activation motif; macrophage; mouse; nonhuman; polarization; protein expression; real time polymerase chain reaction; signal transduction; T lymphocyte activation; Western blotting
Publisher
FRONTIERS MEDIA SA
Type
journal article