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

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.