IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity
Epp Kaleviste, Malte Rühlemann, Jaanika Kärner, Liis Haljasmägi, Liina Tserel, Elin Org, Katarina Trebušak Podkrajšek, Tadej Battelino, Corinna Bang, André Franke, Pärt Peterson, Kai Kisand
Abstract
gene. The hallmark of the disease is the production of highly neutralizing autoantibodies against type I interferons and IL-22. Considering the importance of IL-22 in maintaining mucosal barrier integrity and shaping its microbial community, we sought to study potential changes in the oral cavity in this model of human IL-22 paucity. We found that besides known Th22 cell deficiency, APECED patients have significantly fewer circulating MAIT cells with potential IL-22 secreting capacity. Saliva samples from APECED patients revealed local inflammation, the presence of autoantibodies against IFN-α and IL-22, and alterations in the oral microbiota. Moreover, gene expression data of buccal biopsy samples suggested impaired antimicrobial response and cell proliferation, both of which are processes regulated by IL-22. Our data complement the knowledge gained from mouse models and support the concept of IL-22 being a critical homeostatic cytokine in human mucosal sites.