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

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

Tomoki Sasaki  1 , Hiroyuki Nagashima  2 , Atsushi Okuma  1 , Takeshi Yamauchi  3 , Kenshi Yamasaki  3 , Setsuya Aiba  3 , Takanori So  2 , Naoto Ishii  2 , Yuji Owada  4 , Takashi MaruYama  1   5 , Shuhei Kobayashi  6   7   8
Affiliations

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

Tomoki Sasaki et al. Dig Dis Sci. 2022 Apr.

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.

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