Tomoki Sasaki1, Hiroyuki Nagashima2, Atsushi Okuma1, Takeshi Yamauchi3, Kenshi Yamasaki3, Setsuya Aiba3, Takanori So2, Naoto Ishii2, Yuji Owada4, Takashi MaruYama1,5, Shuhei Kobayashi6,7,8. 1. Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, Sendai, Japan. 2. Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan. 3. Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan. 4. Department of Organ Anatomy, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi, Japan. 5. Mucosal Immunology Unit, NIDCR, NIH, Bethesda, MD, USA. 6. Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, Sendai, Japan. s_kobayashi@med.tohoku.ac.jp. 7. Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan. s_kobayashi@med.tohoku.ac.jp. 8. Department of Organ Anatomy, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-Ku, Sendai, Miyagi, Japan. s_kobayashi@med.tohoku.ac.jp.
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.
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.