Simplified sketch of the Siglec-G–CD24 axis in GVHD. Host hematopoietic APCs express Siglec-G, and donor T cells express CD24. Total body irradiation (TBI) reduces the expression of Siglec-G, reducing its tolerogenic impact. Siglec-G activation on APCs occurs by binding to CD24 from T cells and leads to Src homology 2-containing inositol 5′ phosphatase 1/2 (SHP-1/2) phosphorylation. This in turn dampens the immune response elicited by the DAMP HMGB-1.