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Molecular and Cellular Pediatrics
Fig. 1 | Molecular and Cellular Pediatrics

Fig. 1

From: Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation

Fig. 1

Illustration of the Fas-FasL pathway. Fas (CD95) is a trimeric receptor of the tumor TNF-R family and after binding of the Fas ligand (FasL, CD95L), recruits the adaptor FADD, which in turn forms the so-called DISC together with pro-caspase-8 and pro-caspase-10. Following activation, caspase-8 and caspase-10 then initiate the extrinsic apoptotic pathway leading to proteolysis, DNA degradation, and apoptosis. Mutations in the genes responsible for the Fas-FasL signaling cascade (FAS, FASLG, FADD, CASP10) lead to the development of ALPS. Hallmarks of the disease are increased ALPS biomarkers (Vitamin B12 and sFasL), as well as a massive expansion of double-negative T cells (DNT). Increased AKT/mTOR activation leads to DNT hyperproliferation and can be inhibited via mTOR inhibitors such as sirolimus (rapamycin)

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