RT Journal Article SR Electronic T1 Colitis is associated with loss of LHPP and up-regulation of histidine phosphorylation in intestinal epithelial cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.10.11.334334 DO 10.1101/2020.10.11.334334 A1 Linder, Markus A1 Liko, Dritan A1 Kancherla, Venkatesh A1 Piscuoglio, Salvatore A1 Hall, Michael N. YR 2020 UL http://biorxiv.org/content/early/2020/10/11/2020.10.11.334334.abstract AB Protein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis (1). Using novel monoclonal antibodies to detect pHis (2), we recently reported that loss of the histidine phosphatase LHPP results in elevated pHis levels in hepatocellular carcinoma (3). Here, we show that intestinal inflammation correlates with loss of LHPP, in DSS-treated mice and in inflammatory bowel disease (IBD) patients. Increased histidine phosphorylation was observed in intestinal epithelial cells (IECs), as determined by pHis immunofluorescence staining of colon samples from a colitis mouse model. However, ablation of Lhpp did not cause increased pHis or promote intestinal inflammation in physiological conditions or after DSS treatment. Our observations suggest that increased histidine phosphorylation plays a role in colitis, but loss of LHPP is not sufficient to increase pHis or to cause inflammation in the intestine.Competing Interest StatementThe authors have declared no competing interest.