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

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.