Figure 1.

Pathogenesis of acute GVHD. Conditioning by irradiation and/or chemotherapy causes tissue damage. Damaged tissues and cells release DAMPs (HMGB-1), PAMPs (LPS) from gut microbiota as well as inflammatory cytokines such as IL-1β, IL-6, and TNF-α, which contribute to the “cytokine storm.” These are the first danger signals that activate host APCs, which activate and polarized donor T-cells toward pathogenic T-cells (TH1 and TH17 for CD4 and TC1, TC17 for CD8). Activated pathogenic T-cells infiltrate target organs (i.e., GI tract, liver, skin) and amplify local tissue destruction. The presence of regulatory T-cells (Tregs) helps reduce GVHD severity through the inhibition of pathogenic cells activation and/or expansion at early or further phases of GVHD. Some of these DAMPs and PAMPs such as elafin (skin-specific), regenerating islet-derived 3-alpha (REG3α, gut-specific), and suppressor of tumorigenicity 2 (ST2, a member of the IL-1 receptor family, binding IL-33) have been shown to be biomarkers.