p300 promotes differentiation of Th17 cells via positive regulation of the nuclear transcription factor RORγt in acute respiratory distress syndrome

摘要

Acute respiratory distress syndrome (ARDS) has been the major cause of acute respiratory failure in critical patients and one of the leading causes of death worldwide for several decades. Th17 cells are involved in the occurrence and progression of ARDS. Furthermore, histone acetyltransferase (HAT) p300 is a transcriptional coactivator, and its activity is closely related to cancer and inflammatory diseases. p300 and histone deacetylase 1 (HDAC1) interact with and stabilize the nuclear transcription factor retinoic acid-related orphan receptor gamma t (RORγt) and participate in the regulation of RORγt-mediated IL-17 transcription in T helper 17 (Th17) cell differentiation by acetylation and deacetylation. However, the effect of p300 on RORγt and Th17 cells in ARDS is not well reported. Therefore, we aimed to investigate the clinical features of p300 and its effect on RORγt and Th17 cells in patients with ARDS as well as in lipopolysaccharide-induced acute lung injury (ALI) mouse models. Overexpression of p300 and RORγt mRNA was found in the peripheral blood mononuclear cells from patients with ARDS, especially among non-survivors, compared to that in healthy individuals (P?