Signal-regulatory protein gamma (SIRPG) (SIRPG)

Signal-regulatory protein gamma (SIRPγ), also known as CD172g, is a member of the signal-regulatory protein (SIRP) family and is uniquely expressed on human T lymphocytes and natural killer (NK) cells (UniProt Q9P1W8). Unlike other family members like SIRPα, which acts as an inhibitory receptor on myeloid cells, SIRPγ lacks an inhibitory signaling motif and primarily functions as an adhesion molecule by binding to CD47 (Brooke et al., 2004). This interaction is essential for T-cell transendothelial migration and plays a significant role in co-stimulating T-cell proliferation and cytokine production (Stefanidakis et al., 2008). In the context of oncology, the CD47-SIRPγ axis is a therapeutic target; blocking this interaction can prevent tumor-mediated immune evasion and enhance T-cell infiltration into tumors (Logtenberg et al., 2020). Conversely, in autoimmune diseases, the axis may be targeted to reduce pathological T-cell activation. Most current clinical candidates targeting this pathway are CD47 antagonists or SIRPα-Fc fusion proteins that indirectly modulate SIRPγ signaling by competing for the shared ligand, CD47. A significant challenge in developing SIRPγ-targeted therapies is the lack of a rodent ortholog, which complicates preclinical safety and efficacy studies.

Other names

CD172gSIRP-gammaSignal-regulatory protein beta-2SIRPB2SIRP-beta-2

Antagonism of the CD47-SIRPγ interaction to enhance T-cell mediated anti-tumor immunity or modulate inflammatory responses.