Secretory Leukoprotease Inhibitor (Slpi) Expression Is Required for Educating Murine Dendritic Cells Inflammatory Response Following Quercetin Exposure

Abstract

Dendritic cells’ (DCs) ability to present antigens and initiate the adaptive immune response confers them a pivotal role in immunological defense against hostile infection and, at the same time, immunological tolerance towards harmless components of the microbiota. Food products can modulate the inflammatory status of intestinal DCs. Among nutritionally-derived products, we investigated the ability of quercetin to suppress inflammatory cytokines secretion, antigen presentation, and DCs migration towards the draining lymph nodes. We recently identified the Slpi expression as a crucial checkpoint required for the quercetin-induced inflammatory suppression. Here we demonstrate that Slpi-KO DCs secrete a unique panel of cytokines and chemokines following quercetin exposure. In vivo, quercetin-enriched food is able to induce Slpi expression in the ileum, while little effects are detectable in the duodenum. Furthermore, Slpi expressing cells are more frequent at the tip compared to the base of the intestinal villi, suggesting that quercetin exposure could be more efficient for DCs projecting periscopes in the intestinal lumen. These data suggest that quercetin-enriched nutritional regimes may be efficient for suppressing inflammatory syndromes affecting the ileo-colonic tract.

Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS

“…Host polymorphisms in ubiquitin proteasome system genes have been associated with the risk of IBD 57. This is relevant considering that both microbiota-based58 and non-microbiota-59 60based inhibition of protease activity has been investigated. We also showed that intestinal permeability is higher in mice humanised with high PA stool suggesting that microbiota may regulate intestinal permeability via ineffective inhibition or production of specific intestinal proteases.…”

Quercetin‐Induced miR‐369‐3p Suppresses Chronic Inflammatory Response Targeting C/EBP‐β

“…Quercetin, one of the most common flavonoids present in vegetables and fruits, has been reported to be an anti‐inflammatory substance that possesses a strong anti‐inflammatory ability . This function has been studied in different cell types, in both animal and human models . Additionally, recent work has clearly demonstrated quercetin immunosuppressive effects on dendritic cells function .…”

“…DCs line the gastrointestinal tract epithelial monolayer, continuously sampling the intestinal lumen to present luminal antigen and trigger the adaptive immune response . Intestinal DCs respond to quercetin oral administration by initiating an anti‐inflammatory molecular pathway . Here we demonstrate that miR‐369‐3p is also induced by intestinal resident DCs.…”

Coronavirus Disease (COVID-19–SARS-CoV-2) and Nutrition: Is Infection in Italy Suggesting a Connection?

“…During recent years, our groups, together with several others worldwide, demonstrated the ability of nutritionally derived bioactive compounds to suppress inflammatory cytokine release (40)(41)(42)(43). In particular, the administration of several plant-derived polyphenols to in vitro cultured immune cells suppressed the release of inflammatory cytokines (44).…”