Functional Analysis of the Transcriptional Regulator IκB-ζ in Intestinal Homeostasis

Dig Dis Sci. 2022 Apr;67(4):1252-1259. doi: 10.1007/s10620-021-06958-8. Epub 2021 Apr 5.

Abstract

Background: The Toll-like receptor signaling pathway contributes to the regulation of intestinal homeostasis through interactions with commensal bacteria. Although the transcriptional regulator IκB-ζ can be induced by Toll-like receptor signaling, its role in intestinal homeostasis is still unclear.

Aims: To investigate the role of IκB-ζ in gut homeostasis.

Methods: DSS-administration induced colitis in control and IκB-ζ-deficient mice. The level of immunoglobulins in feces was detected by ELISA. The immunological population in lamina propria (LP) was analyzed by FACS.

Results: IκB-ζ-deficient mice showed severe inflammatory diseases with DSS administration in the gut. The level of IgM in the feces after DSS administration was less in IκB-ζ-deficient mice compared to control mice. Upon administration of DSS, IκB-ζ-deficient mice showed exaggerated intestinal inflammation (more IFN-g-producing CD4+ T cells in LP), and antibiotic treatment canceled this inflammatory phenotype.

Conclusion: IκB-ζ plays a crucial role in maintaining homeostasis in the gut.

Keywords: Gut homeostasis; Inflammatory bowel disease (IBD); IκB-ζ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis* / metabolism
  • Dextran Sulfate / toxicity
  • Homeostasis
  • Humans
  • Interferon-gamma
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction

Substances

  • Interferon-gamma
  • Dextran Sulfate