Epithelial-derived interleukin-23 promotes oral mucosal immunopathology.

At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation.

Transcription factor Tox2 is required for metabolic adaptation and tissue residency of ILC3 in the gut.

Group 3 innate lymphoid cells (ILC3) are the major subset of gut-resident ILC with essential roles in infections and tissue repair, but how they adapt to the gut environment to maintain tissue residency is unclear. We report that Tox2 is critical for gut ILC3 maintenance and function. Gut ILC3 highly expressed Tox2, and depletion of Tox2 markedly decreased ILC3 in gut but not at central sites, resulting in defective control of Citrobacter rodentium infection. Single-cell transcriptional profiling revealed decreased expression of Hexokinase-2 in Tox2-deficient gut ILC3. Consistent with the requirement for hexokinases in glycolysis, Tox2-/- ILC3 displayed decreased ability to utilize glycolysis for protein translation. Ectopic expression of Hexokinase-2 rescued Tox2-/- gut ILC3 defects. Hypoxia and interleukin (IL)-17A each induced Tox2 expression in ILC3, suggesting a mechanism by which ILC3 adjusts to fluctuating environments by programming glycolytic metabolism. Our results reveal the requirement for Tox2 to support the metabolic adaptation of ILC3 within the gastrointestinal tract.

Dog, cat, bird, fish, and other pet ownership and mortality: Evidence from the HILDA cohort.

This study used the nationally representative prospective study of the Household, Income and Labour Dynamics in Australia (HILDA) survey cohort to examine the association of pet ownership (dog, cat, bird, fish, and others) with the risk of all-cause mortality using propensity score matching based on a wide range of factors. The study sample included 15,735 participants who completed the questionnaire on pet ownership in 2018. The HILDA survey sample was matched to the National Death Index through 2022 to assess death during the follow-up period. Statistical analysis was weighted by the inverse of the propensity score in the generalized estimating equation. During the 4-year follow-up period, 377 of 15,735 (2.4%) participants died. The odds ratios (ORs) for all-cause mortality were 0.77 (95%CI: 0.59-0.99) for dog owners compared to non-pet owners after controlling for related socio-demographic, physical, psychological, and social factors. The Sobel test showed a partial mediating effect of physical activity level on the relationship between dog ownership and all-cause mortality. Ownership of cats, birds, fish, and others showed no clear association with mortality, despite owners having similar socio-demographics characteristics to dog owners. Companionship and exercise of a pet dog may be recommended as a component of health promotion policy, and may have an important role to play in promoting health aging.

Dissociation of murine oral mucosal tissues for single cell applications.

Single-cell RNA sequencing and flow cytometry approaches have been instrumental in understanding cellular states within various tissues and organs. However, tissue dissociation methods can potentially alter results and create bias due to preferential recovery of particular cell types. Here we present efforts to optimize methods for dissociation of murine oral mucosal tissues and provide three different protocols that can be utilized to isolate major cell populations in the oral mucosa. These methods can be used both in health and in states of inflammation, such as periodontitis. The optimized protocols use different enzymatic approaches (collagenase II, collagenase IV and the Miltenyi whole skin dissociation kit) and yield preferential recovery of immune, stromal and epithelial cells, respectively. We suggest choosing the dissociation method based on the cell population of interest to study, while understanding the limitations of each approach.

Acceptance of care technologies to support activities of daily living by middle-aged and older adults in Japan: A cross-sectional study.

Background: Various technologies to provide long-term care have been developed in the last decade due to the shortage of caregivers in Japan. However, care technologies are not widely used in long-term care, and the reasons for the lack of acceptance of care technologies are poorly understood. Objectives: To identify the factors associated with the acceptance of care technologies designed to assist with activities of daily living (i.e., bathing, dressing, toileting, transferring, and eating) among middle-aged and older adults in Japan. Design and Methods: A cross-sectional survey was conducted in August 2020. The target population was middle-aged and older adults (i.e., 40-79 years) in Japan. We used an online questionnaire platform of a research company to target people throughout Japan, and measured the acceptance of care technologies to support the performance of each of five activities of daily living. Multivariable logistic regression models were fitted to identify the associated factors using the bivariate variable "willingness to use care technologies for activities of daily living" as the dependent variable. Results: A total of 3261 eligible respondents were included in the analysis. The factors positively associated with the acceptance of care technologies for transferring, which had the highest level of acceptance, were female sex (adjusted odds ratio=1.25, 95% CI: 1.04-1.52), university or higher education level (1.73, 1.41-2.12), an annual income of 39000 to 58999 USD (1.47, 1.08-2.01) or greater than 99,000 USD (1.88, 1.21-2.94), experience as an informal caregiver (1.25, 1.02-1.54), the use of social networking services a few times per year (1.40, 1.11-1.78) or nearly every day (1.47, 1.19-1.82), and willingness to live in a nursing home when care is needed (1.29, 1.05-1.60). In contrast, aged 70-79 years was negatively associated with the acceptance of care technologies for transferring (0.70, 0.52-0.93). Conclusion: Female sex, university or higher education level, an annual income greater than 99,000 USD, the use of social networking services a few times per year or more often, and willingness to live in a nursing home when care is needed were positively associated with the acceptance of care technologies for multiple activities of daily living. Given that many of the respondents will need care in 5-10 years, the acceptance of care technologies among those who need care will increase. Therefore, governments and developers of care technologies could consider the potential needs of this population group.