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 ( PF 4) was the first discovered CXC chemokine and is found in platelet granules at very high concentration. In this study, we provide strong evidence that PF 4 is involved directly in liver innate immune response against IRI by regulating Th17 differentiation. PF 4 deficiency aggravates liver IRI , as shown by higher serum alanine aminotransferase ( ALT ) levels and Suzuki scores. PF 4 deficiency promotes Th17 response with higher levels of IL ‐23, IL ‐6 and IL ‐17, which aggravates liver IRI . Furthermore, PF 4 deficiency limits suppressor of cytokine signalling 3 ( SOCS 3) expressions, and PF 4 fails to suppress expression of IL ‐17 in cells transfected with SOCS 3 Si RNA . In conclusion, PF 4 limits liver IRI through IL ‐17 inhibition via upregulation of SOCS 3.