https://www.selleckchem.com/Proteasome.html We conclude that PTX3 is secreted mainly through conventional protein secretion, and a small percentage of PTX3 is released in exosomes from LPS-stimulated adipocytes. Background Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds yearly without developing systemic reactions. Objective This study aims to analyse the mechanisms underlying bee venom tolerance in beekeepers. A cross-sectional study was conducted. Participants were recruited and classified into three groups allergic patients (AP) experiencing systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBK) receiving ≥50 stings/year; and healthy non-exposed controls (HC). Serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5 and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T-cells (Treg cells) and IL-10 production, were measured. APs had high levels of sIgE to AmV and all its allergic components (p<0.001) together with a high basophil activation rate (p<0.001) compared to TBKs. Conversely, compared to APs, TBKs showed higher levels of sIgG4 (p<0.001) and IL-10 (p<0.001) as well as an enhanced CTLA-4+ Treg population (p=0.001), expanded Helios- Treg (p<0.003), and reduced T-helper 1 (p=0.008), T-helper 2 (p=0.004) and T-helper 17 (p=0.007) subsets. A different profile, strongly marked by Treg activity, was found in TBKs. This natural tolerance would be led by the expansion of inducible Helios-Treg cells at a peripheral level. Helios-Treg population could be a novel candidate biomarker useful for monitoring tolerance. A different profile, strongly marked by Treg activity, was found in TBKs. This natural tolerance would be led by the expansion of inducible Helios-Treg