The JAK Inhibitor Tofacitinib Rescues Intestinal Barrier Defects Caused by Disrupted Epithelial-macrophage Interactions.

ABSTRACT:

Background and aims

Loss-of-function variants in protein tyrosine phosphatase non-receptor type-2 [PTPN2] promote susceptibility to inflammatory bowel diseases [IBD]. PTPN2 regulates Janus-kinase [JAK] and signal transducer and activator of transcription [STAT] signalling, while protecting the intestinal epithelium from inflammation-induced barrier disruption. The pan-JAK inhibitor tofacitinib is approved to treat ulcerative colitis, but its effects on intestinal epithelial cell-macrophage interactions and on barrier properties are unknown. We aimed to determine if tofacitinib can rescue disrupted epithelial-macrophage interaction and barrier function upon loss of PTPN2.

Methods

Human Caco-2BBe intestinal epithelial cells [IECs] and THP-1 macrophages expressing control or PT

SUBMITTER: Spalinger MR 

PROVIDER: S-EPMC7944512 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature