Table 1.
Inflammatory DAMPs and their impact on SOTx outcomes.
| Family | Molecule | Receptors | Role in Tx- related inflammation/immunity/outcomes | References |
|---|---|---|---|---|
| Inflammatory DAMPs | ||||
| Histones | TLR2, TLR4, and TLR9 | Causes TLR- and inflammasome-dependent generation of inflammatory response by innate cells | (6, 8, 9) | |
| HMGB1 | TLR2, TLR4, RAGE, and TIM3 | Promotes the production of pro-inflammatory cytokines and chemokines by innate immune cells Induces metabolic reprogramming supporting the pro-inflammatory functions of myeloid APC Promotion of AR and CR in experimental models Implicated in poor outcomes after clinical transplantation |
(2, 10–15) | |
| IL1α | IL-1R | Promotes the production of pro-inflammatory cytokines and chemokines by innate immune cells | (16) | |
| ATP | P2Y2 and P2X7 | Attraction and activation of innate cells Promotes inflammasome activity Causes the release pro-inflammatory cytokines supporting rejection Promotes IL-1β and IL18 secretion and initiates inflammatory cell death Stimulates alloimmunity |
(6, 17–20) | |
| Vimentin | Dectin-1 | Induces metabolic reprogramming supporting the pro-inflammatory functions of myeloid APC Induces macrophage TNF α and IL-6 production |
(6, 10) | |
| Hyaluronan (HA) | TLR2 and TLR4 | Low molecular weight breakdown products stimulate macrophages pro-inflammatory cytokine production Supports of alloimmunity |
(21–23) | |
| S100s | TLR2, TLR4, RAGE | Potent immunostimulatory activity, monocytes and neutrophils recruitment | (6, 24) | |
| Mitochondrial DNA (mDNA) | TLR9 | Macrophages and neutrophils activation Promotes inflammasome activity Causes the release pro-inflammatory cytokines supporting rejection Promotes IL-1β and IL18 secretion and initiates inflammatory cell death |
(6, 25, 26) |