Table 1.

Proposed Alarmins and Their Impact on Alloimmunity

Alarmin	Receptor	Impact	References
Nuclear Proteins
High-mobility group box 1 (HMGB1)	TLR2, TLR4, RAGE	Promotes Alloreactive T cell responses, GHVD, and Tx rejection Pre-conditioning protects against I/R injury	(34) (40) (39) (35) (36) (37) (38) (46)
IL-1α	IL-1R		(9)
IL-33	ST2	Increases GVHD via augmentation of Type 1 Immunity Supports protection of HTx via Treg expansion	(25) (26, 29)
Cytosolic Materials
Heme	TLR4	Implicated in innate immune cell activation leading to increased alloimmune responses	(12) (19)
Haptoglobin	MyD88-dependent Receptor	Donor Haptoglobin Activates DC to stimulate allograft rejection	(13)
Mitochondria	Formyl Peptide Receptor-1; TLR9	Proposed to activate innate responses after Tx	(11)
ATP	P2X7	Promotes GVHD	(15)
Heat Shock Proteins (HSP)		Promotes alloreactive T cell proliferation and GVHD Modulation of Treg may be protective against I/R	(15) (48)
Extracellular Matrix Materials
Heparan Sulfate	TLR4-My88	Mediates activation of DC to promote alloimmune responses	(15)
Hyaluronan	TLR2/4-My88	Low molecular weight hyaluronan degradation products activates APC to stimulate chemokine and cytokine production, which drives alloimmunity High molecular weight hyaluronan protects against epithelial cell apoptosis and attenuates allograft inflammation.	(51) (52) (53) (50) (51) (53)