Dihydroartemisinin (DHA) is an important derivative of an herb medicine Artemisia annua L., used in ancient China. DHA is currently used world-wide to treat malaria by killing malaria-causing parasites. In addition to this prominent effect, DHA is suggested to regulate cellular functions, such as angiogenesis, tumor cell growth and immunity. Nonetheless, how DHA affects T cell function remains poorly understood. We found that DHA potently suppressed Th cell differentiation in vitro.

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... however, DHA greatly promoted Treg cell generation, in a manner dependent on TGF-βR:Smad signal. In addition, DHA treatment effectively reduced EAE onset and ameliorated ongoing EAE in mice. Administration of DHA significantly decreased Th but increased Treg cells in EAE-inflicted mice without apparent global immune suppression. Moreover, DHA modulated mTOR pathway, because mTOR signal was attenuated in T cells upon DHA treatment. Importantly, enhanced Akt activity neutralized DHA-mediated effects on T cells in an mTOR dependent fashion. This study therefore reveals a novel immune regulatory function of DHA to reciprocally regulate Th and Treg cell generation through modulating mTOR pathway. It addresses how DHA regulates immune function and suggests a new type of drug for treating diseases where mTOR activity to be tempered.