AUTHOR=Kaleviste Epp , Rühlemann Malte , Kärner Jaanika , Haljasmägi Liis , Tserel Liina , Org Elin , Trebušak Podkrajšek Katarina , Battelino Tadej , Bang Corinna , Franke Andre , Peterson Pärt , Kisand Kai TITLE=IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00838 DOI=10.3389/fimmu.2020.00838 ISSN=1664-3224 ABSTRACT=

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by recessive mutations in the AIRE 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.