SLc7a8 is a key amino acids supplier for the metabolic programs that sustain homeostasis and activation of type 2 innate lymphoid cells

Group 2 innate lymphoid cells (ILC2) are innate counterparts of T helper 2 (Th2) cells that maintain tissue homeostasis and respond to injuries through rapid interleukin (IL)-5 and IL-13 secretion. ILC2s depend on availability of arginine and branched-chain amino acids for sustaining cellular fitness, proliferation, and cytokine secretion in both steady state and upon activation. However, the contribution of amino acid transporters to ILC2 functions is not known. Here, we found that ILC2s selectively expres

Predictive factors of age at menopause in a large Australian twin study

Various studies have investigated potential predictors of age at natural menopause but have produced inconsistent results. The relationship between age at natural menopause and socioeconomic, reproductive, and health behavioral factors was evaluated using longitudinal data from 5961 Australian female twins, aged 17 to 88 years at the time of study. The sample consisted of women voluntarily enrolled in the Australian Twin Registry. Failure-time analysis was the principal statistical method used to handle censored observations. Kaplan-Meier estimates showed the overall median age at natural menopause to be 51 years (95% confidence interval, 50-51). Median age at menopause was earlier for women with earlier birth year, women with late age of menarche, women who had no children, or women who were smokers. Differences in age at menopause between social, occupational, and educational groups were statistically significant (Mantel-Cox test, p < 0.001) for education, major occupational classification, combined income, and self-rated social class, with higher age at menopause for higher levels of each variable. A Cox proportional hazards model was used to estimate the odds ratio of the occurrence of natural menopause among different sub-groups, adjusted to reflect simultaneous effects of all other significant covariates. This large study provided clear trends of association in predictors relating to age at menopause. These trends may help to resolve uncertainties and conflicting results identified in studies of comparable white samples. The nature of the twin data also sets a solid background for future analyses of genetic and environmental variance components using statistical modeling or related methods

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4 eosinophils unique to the small intestine

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile