Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain

• DOI: 10.3389/fimmu.2022.890298
• Publication Date: 2022-07-28T14:32:33Z
• Authors: Francesca Gargano; Gisella Guerrera; Eleonora Piras; Barbara Serafini; Monica Di Paola; Lisa Rizzetto; Maria Chiara Busc...; Viviana Annibali; Claudia Vuotto; Marco De Bardi; Silvia D’Orso; Serena Ruggieri; Claudio Gasperini; Lorenzo Pavarini; Giovanni Ristori; Mario Picozza; Barbara Rosicarelli; Clara Ballerini; Rosella Mechelli; Francesco Vitali; Duccio Cavalieri; Marco Salvetti; Daniela F. Angelini; Giovanna Borsellino; Carlotta De Filippo; Luca Battistini
• Keywords: Proinflammatory cytokine

The composition of the intestinal microbiota plays a critical role in shaping immune system. Modern lifestyle, inappropriate use antibiotics, and exposure to pollution have significantly affected commensal microorganisms. has been shown sustain autoimmune responses at distant sites animal models disease, may also immune-mediated central nervous system (CNS) diseases such as multiple sclerosis (MS). We studied gut mycobiota fecal samples from 27 persons with MS (pwMS) 18 healthy donors (HD), including 5 pairs homozygous twins discordant for MS. found tendency towards higher fungal abundance richness group, we observed that showed rate food-associated strains, Saccharomyces cerevisiae . then pwMS, distinct population cells antibacterial antifungal activity is expanded during remitting phase markedly decreases clinically and/or radiologically active disease. These cells, named MAIT (mucosal-associated invariant T cells) lymphocytes, were more activated pwMS compared HD response S. Candida albicans strains isolated samples. This activation was mediated by fungal-induced IL-23 secretion innate cells. Finally, immunofluorescent stainings post-mortem brain tissues secondary progressive form disease cross blood–brain barrier (BBB) produce pro-inflammatory cytokines brain. results agreement hypothesis dysbiosis might determine subset pathogenic mucosal favor development systemic inflammatory diseases.