HMGB1
The innate cells plays a critical role during organ transplantation to initiate the immune recognition and response against the allograft, mediate chronic rejection and exhibit features of trained immunity. Here we found that HMGB1 could induce DC trained immunity. These trained DCs have more powerful alloantigen presenting capacity to promote T cell function and proliferation, by high level of MHC II and class II major histocompatibility complex transactivator (CIITA) molecule up to 2 weeks later. Further epigenetic assay show that the histone of MHC II and CIITA locus region was highly acetylated in trained DCs. Beyond known promoters of CIITA, we identified a regulatory region of CIITA, which formed super enhancer to promote CIITA transcription and DC trained immunity. CIITA SE inhibition impaired DC trained immunity and prolonged allograft survival. Together, our finding and strategy focus on SE and innate trained immunity reveals the mechanism of immune response initialing and maintaining in chronic rejection, provides potential target for induction of immunological tolerance and allograft acceptance.