3-O-acetyl-11-keto-beta-boswellic acid (β-AKBA) and 11-keto-beta-boswellic acid (β-KBA) increase FoxP3 expression in CD4+ T regulatory cells

Abstract

Boswellic acids (BAs) have multiple beneficial effects against inflammatory and autoimmune diseases. However, their immunomodulatory activities are poorly understood. Herein, we investigated whether individual compounds of BAs including β-BA, β-KBA, and β-AKBA extracted from Boswellia sacra, have any potential effects on the phenotype of human T regulatory cells (Tregs), by analyzing the expression of Treg markers including FoxP3 and Helios transcription factors. Importantly, β-KBA and β-AKBA at 25 μM concentration induced a significant increase in FoxP3 expression in CD4⁺ Tregs. Additionally, treatment of stimulated T cells with β-BA, β-KBA, and β-AKBA increased FoxP3 expression in CD8⁺ T cells, but without any statistical significance. By investigating co-expression levels of FoxP3 and Helios in CD4⁺ T cells, we did not find any significant differences in the levels of CD4⁺FoxP3⁺Helios⁺ Tregs. Interestingly, significant increases in levels of CD4⁺FoxP3⁺Helios^- Tregs were observed following treatment with β-KBA and β-AKBA. Our findings show that β-KBA and β-AKBA have the potential to increase FoxP3 expression in CD4⁺ Tregs in vitro. Clearly, further in vivo investigations, in addition to the mechanism of action of β-KBA and β-AKBA on FoxP3 expression, are required to gain a deeper understanding of the beneficial effects of these compounds for treating autoimmune and inflammatory diseases.

Keywords: Boswellia sacra; FoxP3; Helios; Tregs; β-AKBA; β-KBA.