Figure 8.

A model to illustrate the proapoptotic potential of SARM following T-cell immune response. Antigen presenting cells (APC) present the epitopes of the foreign pathogens to the T cells. Antigen-specific T cells undergo clonal expansion and differentiate into effector T cells. These T cells mediate pathogen clearance. Later, apoptosis specifically contracts the expanded T cells in a well-orchestrated manner. Our influenza infection mouse model demonstrates the proapoptotic function of SARM during T-cell contraction. SARM expression is significantly decreased during activation-induced T-cell clonal expansion to support proliferation. During T-cell contraction, SARM is elevated and it acts proapoptotically via intrinsic pathway. SARM seems to oppose the survival signal mediated by ERK phosphorylation, and modulates the levels of the anti-apoptotic Bcl-xL, leading to the loss of mitochondrial integrity via BAX BAK and ROS. The release of the mitochondrial content leads to activation of the initiator caspase-9 and effector caspase-3. Activated caspases cause apoptosis, thereby bringing down the number of T cells. Failure of T-cell contraction may result in lymphoproliferative diseases and autoimmunity. Coincidently, the expression of proapoptotic SARM is reduced in NK/T lymphoma tissues compared with the healthy cells