Activation of the innate immune system by the endogenous ligand hyaluronan

Endogenous ligands are released during ischemia-reperfusion injury that occurs during organ transplantation. Evidence suggests that these ligands, such as hyaluronan, activate the innate immune system via Toll-like receptors. This review will highlight the studies on the role of hyaluronan in modulating alloimmune responses.

Within the last year, the role of hyaluronan as an endogenous activator of innate alloimmunity has been investigated. We have shown that hyaluronan activates dendritic cells and primes T-cell alloimmunity primarily via a toll like receptor 4/Tirap-dependent pathway. Recent studies have described that the hyaluronan receptor, CD44, modulates these innate immune responses by augmenting regulatory T-cell function, and augmenting the expression of negative regulators of Toll-like receptor signaling.

Hyaluronan activates innate alloimmune responses and subsequently influences adaptive alloimmunity. Improving our understanding of the nature of endogenous innate ligands that activate alloimmunity may lead to improved therapeutics in organ transplantation.