The ability to tolerate Candida albicans, a human commensal of the gastrointestinal tract and vagina, implicates that host defense mechanisms of resistance and tolerance cooperate to limit fungal burden and inflammation at the different body sites. We evaluated resistance and tolerance to the fungus in experimental and human vulvovaginal candidiasis (VVC) as well as in recurrent VVC (RVVC). Resistance and tolerance mechanisms were both activated in murine VVC, involving IL-22 and IL-10-producing regulatory T cells, respectively, with a major contribution by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 was responsible for the production of tolerogenic kynurenines, such that replacement therapy with kynurenines restored immunoprotection to VVC. In humans, two functional genetic variants in IL22 and IDO1 genes were found to be associated with heightened resistance to RVVC, and they correlated with increased local expression of IL-22, IDO1 and kynurenines. Thus, IL-22 and IDO1 are crucial in balancing resistance with tolerance to Candida, their deficiencies are risk factors for RVVC, and targeting tolerance via therapeutic kynurenines may benefit patients with RVVC.

Objectives To evaluate tooth movements during maxillary arch expansion with clear aligner treatment. Materials and Methods The study group included 28 subjects (16 females, 12 males, mean age 31.9 ± 5.4 years) collected prospectively from January 2018 to May 2019. Inclusion criteria were European ancestry, posterior transverse discrepancy of 3–6 mm, permanent dentition stage, presence of second permanent molars, mild or moderate crowding, and good compliance with aligners. Treatment protocol included nonextraction strategies, application of Invisalign clear aligner system, and no auxiliaries other than Invisalign attachments. Linear and angular measurements were performed before treatment (T1), at the end of treatment (T2), and on final virtual models (T2 ClinCheck). A paired t-test was used to compare T2-T1 and T2-T2 ClinCheck changes. The level of significance was set at 5%. Results Statistically significant differences were found for all measurements, except for ones at the upper second molars. The greatest increase in maxillary width was detected at the upper first and second premolars: +3.5 mm for the first premolar and +3.8 mm for the second premolar at T2. Comparison of T2-T1 angular outcomes showed statistically significant changes in the inclinations of all teeth except for the second permanent molars. T2-T2 ClinCheck showed significant differences for both linear and angular measurements for maxillary canines, resulting in poor predictability. Conclusions Maxillary arch development revealed a progressive reduction of the expansion rate and buccal tipping in the anterior, lateral, and posterior regions, with the greatest net increase at the first and second premolars. Clinical attention should be paid to maxillary canine movements, and overcorrection should be planned for them during dentoalveolar expansion.

Periodontitis (PD) is a chronic disease caused by the host inflammatory response to bacteria colonizing the oral cavity. In addition to tolerance to oral microbiome, a fine-tuned balance of IL-10 levels is critical to efficiently mount antimicrobial resistance without causing immunopathology. Clinical and animal studies support that adaptive T-helper (Th) cytokines are involved in the pathogenesis of alveolar bone destruction in PD. However, it remains unclear what type of Th response is related to human PD progression and what role IL-10 has on this process. We addressed the contribution of IL-10 in limiting Th1 and Th17 inflammatory response in murine and human PD. Through a combination of basic and translational approaches involving selected cytokine-deficient mice as well as human genetic epidemiology, our results demonstrate the requirement for IL-10 in fine-tuning the levels of Th17 (IL-17A and IL-17F) cytokines in experimental and human PD. Of novelty, we found that IL-17F correlated with protection in murine and human PD and was positively regulated by IL-10. To our knowledge, this is the first demonstration of the protective role for IL-17F in PD, its positive regulation by IL-10, and the potential differential role for IL-17A and IL-17F in periodontal disease.

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