Contribution of the appendix to ulcerative colitis by supplying pathogenic immunoglobulin G-producing cells

doi:10.3748/wjg.117897

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jul 21, 2026; 32(27): 117897
Published online Jul 21, 2026. doi: 10.3748/wjg.117897

Contribution of the appendix to ulcerative colitis by supplying pathogenic immunoglobulin G-producing cells

Yusuke Izutani, Takayuki Ogino, Shuhei Sakakibara, Yosuke Kishi, Yu-Chen Liu, Yusuke Nakano, Akio Fukada, Yuki Sekido, Ryuichi Kuwahara, Takako Kihara, Mitsunobu Takeda, Tsuyoshi Hata, Atsushi Hamabe, Norikatsu Miyoshi, Mamoru Uemura, Hiroki Ikeuchi, Seiichi Hirota, Kiyoshi Takeda, Tsunekazu Mizushima, Daisuke Okuzaki, Yuichiro Doki, Hidetoshi Eguchi

Yusuke Izutani, Takayuki Ogino, Yusuke Nakano, Akio Fukada, Yuki Sekido, Mitsunobu Takeda, Tsuyoshi Hata, Atsushi Hamabe, Norikatsu Miyoshi, Mamoru Uemura, Yuichiro Doki, Hidetoshi Eguchi, Department of Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan

Shuhei Sakakibara, Laboratory of Systems Immunology, Immunology Frontier Research Center, The University of Osaka, Suita 565-0871, Japan

Yosuke Kishi, Yu-Chen Liu, Daisuke Okuzaki, Laboratory of Human Immunology (Single Cell Genomics), Immunology Frontier Research Center, The University of Osaka, Suita 565-0871, Japan

Ryuichi Kuwahara, Hiroki Ikeuchi, Division of Inflammatory Bowel Disease Surgery, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya 663-8501, Japan

Takako Kihara, Seiichi Hirota, Department of Diagnostic Pathology, Hyogo Medical University, Nishinomiya 663-8501, Japan

Kiyoshi Takeda, Laboratory of Mucosal Immunology, Immunology Frontier Research Center, Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, The University of Osaka, Suita 565-0871, Japan

Tsunekazu Mizushima, Department of Colorectal Surgery, Dokkyo Medical University, Mibu 321-0293, Japan

Co-corresponding authors: Takayuki Ogino and Shuhei Sakakibara.

Author contributions: Izutani Y, Ogino T, Sakakibara S, Kishi Y, Liu YC, Nakano Y, Fukada A, Mizushima T, and Okuzaki D were responsible for formal analysis and investigation, writing original draft preparation; Izutani Y, Ogino T, Sakakibara S, and Okuzaki D were responsible for conceptualization and methodology; Ogino T was responsible for funding acquisition; Ogino T, Sekido Y, Kuwahara R, Kihara T, Takeda M, Hata T, Hamabe A, Miyoshi N, Uemura M, Ikeuchi H, and Hirota S were responsible for resources; Ogino T, Takeda K, Mizushima T, Doki Y, and Eguchi H were responsible for supervision; Izutani Y, Ogino T, Sakakibara S, Kishi Y, Liu YC, Nakano Y, Fukada A, Sekido Y, Kuwahara R, Kihara T, Takeda M, Hata T, Hamabe A, Miyoshi N, Uemura M, Ikeuchi H, Hirota S, Takeda K, Mizushima T, Okuzaki D, Doki Y, and Eguchi H were responsible for writing review and editing; and all authors read and approved the final manuscript.

Supported by the Japan Society for the Promotion of Science KAKENHI, No. 23K08192; Japan Research Foundation for Clinical Pharmacology; Princess Takamatsu Cancer Research Fund; and Japanese Society for Inflammatory Bowel Disease Grants-in-Aid for Inflammatory Bowel Disease Research.

Institutional review board statement: This study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committees of Osaka University School of Medicine (No. 10261) and Hyogo Medical University (No. 0407).

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

Data sharing statement: Data will be shared upon request from the corresponding authors. The raw data of this study were submitted under the Gene Expression Omnibus accession number GSE284191.

Corresponding author: Takayuki Ogino, MD, PhD, Department of Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, 2-2 Yamadaoka, Suita 565-0871, Japan. togino04@gesurg.med.osaka-u.ac.jp

Received: December 18, 2025
Revised: January 21, 2026
Accepted: April 8, 2026
Published online: July 21, 2026
Processing time: 198 Days and 20.8 Hours

Abstract

BACKGROUND

Appendectomy reduces the occurrence and controls the severity of ulcerative colitis (UC); however, how it exerts these effects remains unclear.

AIM

To elucidate the contribution of appendix-associated immune responses in intestinal inflammation and their relevance to the effects of appendectomy in UC.

METHODS

This study was conducted at Graduate School of Medicine, The University of Osaka. We included patients undergoing surgery for UC and those without inflammatory bowel disease undergoing colorectal cancer surgery as controls. Appendiceal tissues were collected from both patient groups, and macroscopically normal appendices located at least 10 cm from the tumor were used as controls. Single-cell RNA sequencing, immunohistochemistry, and flow cytometry were performed.

RESULTS

Single-cell RNA sequencing identified T, B, plasma, innate lymphoid, and mast cells, together with other myeloid cells in appendiceal tissues. A hallmark feature of the appendices in UC was an increase in immunoglobulin G (IgG)-expressing plasma cells. Immunohistochemistry revealed significantly reduced IgG levels in the large intestines of patients with UC who had undergone an appendectomy compared with levels in those who did not undergo appendectomy. Repertoire analysis revealed an increased production of IgG antibodies bearing an integrin-binding motif at antigen-recognition sites in patients with UC.

CONCLUSION

The appendix is a major site of pathogenic IgG antibody production in patients with UC, providing the immunological basis for appendectomy as a treatment for UC.

Keywords: Ulcerative colitis; Appendix; Appendectomy; Autoantibody; Immunoglobulin G

Core Tip: The appendix is a potential source of pathogenic immunoglobulin G (IgG)-producing cells in patients with ulcerative colitis (UC). Appendectomy significantly reduced IgG-positive cells in the large intestine of patients with UC. Appendectomy may alleviate UC symptoms by limiting the number of pathogenic IgG-secreting cells.