Summary Glycosylceramides in mammalian species are thought to be present in the form of β-anomers. This conclusion was reinforced by the identification of only one glucosylceramide and one galactosylcerhamide synthase, both β-transferases, in mammalian genomes. Thus, the possibility that small amounts of α-anomers could be produced by an alternative enzymatic pathway, by an unfaithful enzyme, or spontaneously in unusual cellular compartments has not been examined in detail. We approached the question by taking advantage of the exquisite specificity of T and B lymphocytes and combined it with the specificity of catabolic enzymes of the sphingolipid pathway. Here, we demonstrate that mammalian immune cells produce constitutively very small quantities of α-glycosylceramides, which are the major endogenous ligands of natural killer T cells. Catabolic enzymes of the ceramide and glycolipid pathway tightly control the amount of these α-glycosylceramides. The exploitation of this pathway to manipulate the immune response will create new therapeutic opportunities.

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Background: Both chronic and acute heat result in a substantial health burden globally, causing particular concern for at-risk populations, such as older adults. Outdoor temperatures are often assessed as the exposure and are used for heat warning systems despite individuals spending most of their time indoors. Many studies use ecological designs, with death or hospitalizations rates. Individual-level outcomes that are directly related to heat-symptoms should also be considered to refine prevention efforts. Objectives: In this longitudinal study, we assessed the association between indoor temperature and proximal symptoms in individuals of age living in non–air-conditioned households in Montérégie, Quebec, during the 2017–2018 summer months. Methods: We gathered continuously measured indoor temperature and humidity from HOBO sensors and repeated health-related questionnaires about health-related symptoms administered across three periods of increasing outdoor temperatures, where the reference measurement (T1) occurred during a cool period with a target temperature of 18–22°C and two measurements (T2 and T3) occurred during warmer periods with target temperatures of 28–30°C and 30–33°C, respectively. We used generalized estimating equations with Poisson regression models and estimated risk ratios (RRs) between temperature, humidity, and each heat-related symptom. Results: Participants ( ) had an average age of . Higher indoor temperatures were associated with increased risk of dry mouth (T3 ; 95% CI: 1.8, 3.5), fatigue ( ; 95% CI: 1.8, 3.0), thirst ( ; 95% CI: 2.5, 4.5), less frequent urination ( ; 95% CI: 1.8, 7.3), and trouble sleeping ( ; 95% CI: 1.6, 3.2) compared with T1. We identified a nonlinear relationship with indoor temperatures across most symptoms of interest. Discussion: This study identified that increasing indoor temperatures were associated with various health symptoms. By considering the prevalence of these early stage outcomes and indoor temperature exposures, adaptation strategies may be improved to minimize the burden of heat among vulnerable communities. https://doi.org/10.1289/EHP10291