Artemotil mediates protection in experimental colitis through the induction of Type 1 regulatory T cells

Abstract

Abstract Artemotil (β-arteether) is a semi-synthetic derivative of artemisinin - a natural compound isolated from the plant Artemisia annuaand used worldwide as a front-line anti-malarial drug. Besides its anti-malarial effect, several studies have reported its potential use as an anti-tumor and anti-inflammatory agent. Artemotil was found to suppress the generation and function of Th1 and Th17 while promoting the generation of Foxp3+ regulatory T cells (Tregs). The role of Artemotil in modulating the generation and functions of Type 1 regulatory T cells is not yet identified. Tr1 cells are one of the key cell types that are essential for inhibiting inflammatory response through IL-10. In this study, we report an additional role of Artemotil by selectively inducing the generation of Tr1 cells induced by IL-27 by upregulating the signature of Tr1 cells genes such as c-maf and Prdm1, IRF-1, and Batf. We found that co-administer of Artemotil with anti-CD3 antibody increases the induction of IL-10 and frequency of Tr1 cells while suppressing Th1 and Th17 cells in vivo associated with less severe T-cell-induced enteropathy and intestinal inflammation. We further show the anti-inflammatory role of Artemotil in the chronic T-cell-induced colitis model in which Artemotil treatment alleviates the signs of colitis associated with the increased frequencies of Tr1 cells. Taken together, these data suggest that Artemotil provides protection in T-cell-mediated colitis by increasing the expansion of Tr1 cells and inhibiting the generation of Th1 and Th17 cells. This study was supported by grants from Science & Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India (CRG/2018/002653)