PF4 promotes CXCR3+ Tfh1 cell differentiation through STAT1 in mouse immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by low platelet counts. The mechanism of ITP is complex and remains incompletely understood, but loss of self-tolerance and immune cell dysfunction are associated with this disease. Platelet factor 4 (PF4) is released by activated platelets and has several other biological functions, including leucocyte activation and differentiation. In this study, we detected significant upregulation of PF4 expression in the serum and spleen of ITP mice and the expansion of CXCR3+ type I follicular helper T (Tfh1) cells. An in vitro study revealed that the administration of recombinant PF4 protein in combination with IL-12 synergistically promoted the differentiation of naïve CD4+ T cells into Tfh1 cells through the STAT1 pathway. In this study, we identified the role of PF4 in activating Tfh1 cell differentiation and expansion and eventually promoting the pathogenesis of ITP.