Frontiers in Immunology (Feb 2023)

The protein kinase R modifies gut physiology to limit colitis

  • Howard Chi Ho Yim,
  • Howard Chi Ho Yim,
  • Arindam Chakrabarti,
  • Sean Kessler,
  • Hiroyuki Morimoto,
  • Hiroyuki Morimoto,
  • Die Wang,
  • Die Wang,
  • Dhanya Sooraj,
  • Dhanya Sooraj,
  • Afsar U. Ahmed,
  • Afsar U. Ahmed,
  • Carol de la Motte,
  • Robert H. Silverman,
  • Bryan RG. Williams,
  • Bryan RG. Williams,
  • Anthony J. Sadler,
  • Anthony J. Sadler,
  • Anthony J. Sadler

DOI
https://doi.org/10.3389/fimmu.2023.1106737
Journal volume & issue
Vol. 14

Abstract

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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.

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