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. 2021 Aug 3;22(15):8349.
doi: 10.3390/ijms22158349.

Quercetin Administration Suppresses the Cytokine Storm in Myeloid and Plasmacytoid Dendritic Cells

Giulio Verna  1 , Marina Liso  2 , Elisabetta Cavalcanti  2 , Giusy Bianco  2 , Veronica Di Sarno  1 , Angelo Santino  3 , Pietro Campiglia  1 , Marcello Chieppa  2
Affiliations

Quercetin Administration Suppresses the Cytokine Storm in Myeloid and Plasmacytoid Dendritic Cells

Giulio Verna et al. Int J Mol Sci. .

Abstract

Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin's effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs (Slpi, Hmox1, and AP-1).

Keywords: cytokines; dendritic cells; plasmacytoid; quercetin; slpi.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative density plots for dendritic cells (DCs) found in Peyer’s patches (PP) from wild-type (WT) (A) and Winnie mice (B), and in mesenteric lymphnodes (MLNs) from WT (D) and Winnie (E); 20,000 cells were acquired per each condition. Graphs represent percentages of the different populations of DCs in PP (C) and MLNs (F) in WT and Winnie mice; bars represent mean relative expression ± SEM (n = 4) for each genotype. * p < 0.05 **** p < 0.0001.
Figure 2
Figure 2
Representative density plots for CD11c, B220, and Ly6C staining in mDCs (A), myeloid dendritic cells (mDCs) stimulated with lipopolysaccharide (LPS) for 24 h (B), plasmacytoid dendritic cells (pDCs) (C), pDCs stimulated with LPS for 24 h (D). Bar plots for mean ± SEM (n = 4) showing the percentages of CD11c+B220+Ly6C+ cells (E), CD11c+CD80+ cells (F), and major histocompatibility complex II (MHCII) MFI (mean fluorescence intensity) (G) in control and after LPS stimulation for 24 h. Bar plots representing the mean ± SEM (n = 6) of toll-like receptor 4 (Tlr4) gene expression relative to control mDCs (H). * p < 0.05 *** p < 0.001 **** p < 0.0001.
Figure 3
Figure 3
Bar plots expressing the mean ± SEM (n = 4) for MHCII MFI and CD80 expression (A,B) and 7-Aminoactinomycin D (7-AAD) vitality staining (C) of mDCs and pDCs in baseline conditions and after stimulation with LPS and/or quercetin. *** p < 0.001 **** p < 0.0001.
Figure 4
Figure 4
Scatter plots expressing the mean ± SEM (n = 5) for secreted cytokines of mDCs and pDCs in baseline conditions and after stimulation with LPS and/or quercetin. * p < 0.05 ** p < 0.005 *** p < 0.001 **** p < 0.0001; $ p < 0.05 $$ p < 0.005 $$$ p < 0.001 $$$$ p < 0.0001; * LPS vs. quercetin + LPS; $ mDCs vs. pDCs.
Figure 5
Figure 5
Scatter plots expressing the mean ± SEM (n = 5) for secreted chemokines of mDCs and pDCs in baseline conditions and after stimulation with LPS and/or quercetin. * p < 0.05 *** p < 0.001 **** p < 0.0001; $$$ p < 0.001 $$$$ p < 0.0001; * LPS vs. quercetin + LPS; $ mDCs vs. pDCs.
Figure 6
Figure 6
Scatter plots expressing the mean ± SEM (n = 5) for secreted growth factors of mDCs and pDCs in baseline conditions and after stimulation with LPS and/or quercetin. **** p < 0.0001; $ p < 0.05 $$$$ p < 0.0001; * LPS vs. quercetin + LPS; $ mDCs vs. pDCs.
Figure 7
Figure 7
Molecular pathways activated in mDCs and pDCs 6 h after LPS stimulation and/or quercetin administration. Bar plots representing the mean ± SEM (n = 6) of each gene expression relative to control mDCs. * p < 0.05 ** p < 0.005 **** p < 0.0001; $$ p < 0.005 $$$ p < 0.001 $$$$ p < 0.0001; * LPS vs. quercetin + LPS; $ mDCs vs. pDCs.
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