The protein kinase R modifies gut physiology to limit colitis

Front Immunol. 2023 Feb 17:14:1106737. doi: 10.3389/fimmu.2023.1106737. eCollection 2023.


Here we investigate the function of the innate immune molecule protein kinase R (PKR) in intestinal inflammation. To model a colitogenic role of PKR, we determine the physiological response to dextran sulfate sodium (DSS) of wild-type and two transgenic mice strains mutated to express either a kinase-dead PKR or to ablate expression of the kinase. These experiments recognize kinase-dependent and -independent protection from DSS-induced weight loss and inflammation, against a kinase-dependent increase in the susceptibility to DSS-induced injury. We propose these effects arise through PKR-dependent alteration of gut physiology, evidenced as altered goblet cell function and changes to the gut microbiota at homeostasis that suppresses inflammasome activity by controlling autophagy. These findings establish that PKR functions as both a protein kinase and a signaling molecule in instituting immune homeostasis in the gut.

Keywords: autophagy; colitis; goblet cells; gut barrier; inflammasomes; inflammation; protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy
  • Colitis*
  • Homeostasis
  • Inflammation
  • Mice
  • Mice, Transgenic
  • Protein Kinases


  • Protein Kinases