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

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

doi:10.3390/ijms22158349

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).

Highlights

W CutlerMicrobial or microbial component translocation through the intestinal mucosa can result in dendritic cell (DC) activation and inflammatory cytokines secretion [1]; this response needs to be limited to facilitate tissue repair and a return to intestinal homeostasis; if prolonged, chronic inflammation may arise and progress toward inflammatory bowel diseases (IBDs) [2,3,4]
When gated on CD11c+ cells, FACS data revealed that B220+ plasmacytoid dendritic cells (pDCs) and B220- conventional dendritic cells presence was similar in WT
Winnie Peyer’s patches (PP) (Figure 1C), but we observed a significant increase in CD11c+ B220- CD8monocyte-derived dendritic cells in Winnie mesenteric lymph nodes (MLNs) compared to their WT counterparts (Figure 1D–F)

Summary

Introduction

W CutlerMicrobial or microbial component translocation through the intestinal mucosa can result in dendritic cell (DC) activation and inflammatory cytokines secretion [1]; this response needs to be limited to facilitate tissue repair and a return to intestinal homeostasis; if prolonged, chronic inflammation may arise and progress toward inflammatory bowel diseases (IBDs) [2,3,4]. DCs residing in the gut-associated lymphoid tissues (GALT) are involved in the maintenance of tolerance toward the commensal microbiota that has a pivotal role in the development of IBDs [5]. Two populations of DCs can be distinguished: myeloid (mDCs) and plasmacytoid DCs (pDCs) [10,11] The former are derived from myeloid progenitors that are present in peripheral organs and act as antigen-presenting cells, they secrete pro- and anti-inflammatory cytokines to answer to external stimuli and drive other immune cells toward an effector [12] or tolerogenic response [13]. PDCs derive from lymphoid progenitors and are involved in the production of type

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Conclusion