Background: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. Methods: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. Results: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. Conclusions: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.

Food allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23 ⁺ IgG1 ⁺ memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These ‘type2-marked’ IgG1 ⁺ memory B cells differentially express IL-4/IL-13 regulated genes FCER2 / CD23, IL4R , and germline IGHE and carry highly mutated B cell receptors (BCRs). Further, high affinity memory B cells specific for the main peanut allergen Ara h 2 mapped to the population of ‘type2-marked’ IgG1 ⁺ memory B cells and included convergent BCRs across different individuals. Our findings indicate that CD23 ⁺ IgG1 ⁺ memory B cells transcribing germline IGHE are a unique memory population containing precursors of pathogenic IgE. One-Sentence Summary: We describe a unique population of IgG ⁺ memory B cells poised to switch to IgE that contains high affinity allergen-specific clones in peanut allergy.