In cell-mediated immune responses, T cells play a central role. Their activation is associated with autoimmunity and cancer defense mechanisms. Adelheid Weidinger and Andrey Kozlov from the LBI Trauma’s Research Group for Molecular Basis of Organ Failure and Regeneration, together with the group of Josef Penninger from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (Shane JF Cronin, first author), looked into the mechanisms regulating the activity of T-cells and discovered the critical role of tetrahydrobiopterin (BH4) in these mechanisms. Their findings have just been published in Nature.
The scientists revealed that BH4 is required for the effective proliferation of T cells and can be manipulated to influence autoimmunity or anticancer immunity. As BH4 is required for T-cell-driven autoimmunity, blocking its synthesis could be a way to hold auto-aggressive T cells at bay. On the other hand, BH4 inhibition links the immunosuppressive tumor environment to impaired T cell function. Increasing BH4 levels can overcome this inhibition to counteract tumor growth and enhance antitumor immunity.