Figure 2.

ASM determinates Th responses. Upon stimulations of TCR and CD28 by MHC or antibody ligation, ASM is activated to mediate T-cell activation, whereas PI3K-Akt signaling, likely downstream of CD28 pathways, dampens Treg generation. Meanwhile, a variety of membrane receptors inclusive of CD161, CD39, and perhaps some cytokine receptors, interact with ASM. Once those membrane receptors ligated by their ligands/cytokines, ASM/ceramide signals become activated, and initiate the key pathways which are indispensible for T-cell differentiation and pathogenic Th responses