Prolongation of allograft survival by artemisinin treatment is associated with blockade of OX40-OX40L

Abstract

Objectives

It has been demonstrated that artemisinin (ART) possesses multiple immune modulatory effects. However, its role as immunosuppressant in allogeneic transplantation is undetermined. Here, we investigated the effect of ART on co-stimulatory signaling in OX40⁺ T cells and evaluated ART as a potential immunosuppressant in transplantation.

Materials and methods

Allogeneic skin transplantation was performed in C57BL/6 to BALB/c mice. Recipient mice were administrated with vehicle, ART or cyclosporine A daily from day 0 to day 19 post transplantation. Proportions of splenic CD4⁺OX40⁺ and CD4⁺CD44^hiCD62L^hi cells, and serum IgG was measured by using flow cytometry. An in vitro lymphocyte stimulation with Con A or LPS under various concentrations of ART was performed, expression of CD4⁺OX40⁺ and CD4⁺CD44^hiCD62L^hi cells was evaluated, and interleukin(IL)-6 production was measured by ELISA.

Results

In in vivo allogeneic skin transplant model, ART significantly prolongs allogeneic skin survival. Furthermore, our in vitro studies demonstrate that the immune suppression of ART on T cells is associated with a reduction in OX40⁺ T cells and inhibition of IL-6 secretion.

Conclusion

Our data indicate that the OX40-OX40L pathway and IL-6 are possibly involved in ART-induced immunosuppression, and ART is a potential novel immunosuppressant.

Keywords:

• Artemisinin
• allogeneic transplantation
• OX40
• memory T cells
• IL-6

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Sun Yat-Sen University [Talent Program 2016] and The High Level Health Team on Innovation Research of Zhuhai [2018].