Platelet factor 4 limits Th17 differentiation and ischaemia-reperfusion injury after liver transplantation in mice

Liver ischaemia/reperfusion injury (IRI) is a serious pathologic process encountered in a number of clinical syndromes including liver transplantation, liver resection, trauma and haemorrhagic shock. Platelet factor 4 (PF4) was the first discovered CXC chemokine and is found in platelet granules at very high concentration. In this study, we provide strong evidence that PF4 is involved directly in liver innate immune response against IRI by regulating Th17 differentiation. PF4 deficiency aggravates liver IRI, as shown by higher serum alanine aminotransferase (ALT) levels and Suzuki scores. PF4 deficiency promotes Th17 response with higher levels of IL-23, IL-6 and IL-17, which aggravates liver IRI. Furthermore, PF4 deficiency limits suppressor of cytokine signalling 3 (SOCS3) expressions, and PF4 fails to suppress expression of IL-17 in cells transfected with SOCS3 SiRNA. In conclusion, PF4 limits liver IRI through IL-17 inhibition via upregulation of SOCS3.