Targeting Staphylococcal Enterotoxin B Binding to CD28 As a New Strategy for Dampening Superantigen-mediated Intestinal Epithelial Barrier Dysfunctions

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Mar 21

PMID 38510259

Authors

Carola Amormino

Emanuela Russo

Valentina Tedeschi

Maria Teresa Fiorillo

Alessandro Paiardini

Francesco Spallotta

Laura Rosano

Loretta Tuosto

Martina Kunkl

Affiliations

Soon will be listed here.

Abstract

is a gram-positive bacterium that may cause intestinal inflammation by secreting enterotoxins, which commonly cause food-poisoning and gastrointestinal injuries. Staphylococcal enterotoxin B (SEB) acts as a superantigen (SAg) by binding in a bivalent manner the T-cell receptor (TCR) and the costimulatory receptor CD28, thus stimulating T cells to produce large amounts of inflammatory cytokines, which may affect intestinal epithelial barrier integrity and functions. However, the role of T cell-mediated SEB inflammatory activity remains unknown. Here we show that inflammatory cytokines produced by T cells following SEB stimulation induce dysfunctions in Caco-2 intestinal epithelial cells by promoting actin cytoskeleton remodelling and epithelial cell-cell junction down-regulation. We also found that SEB-activated inflammatory T cells promote the up-regulation of epithelial-mesenchymal transition transcription factors (EMT-TFs) in a nuclear factor-κB (NF-κB)- and STAT3-dependent manner. Finally, by using a structure-based design approach, we identified a SEB mimetic peptide (pSEB) that, by blocking the binding of SEB to CD28, dampens inflammatory-mediated dysregulation of intestinal epithelial barrier.

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