Review
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2024; 30(1): 34-49
Published online Jan 7, 2024. doi: 10.3748/wjg.v30.i1.34
Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data
Yu-Wei Zhou, Yue Ren, Miao-Miao Lu, Ling-Ling Xu, Wei-Xin Cheng, Meng-Meng Zhang, Lin-Ping Ding, Dong Chen, Jian-Guo Gao, Juan Du, Ci-Liang Jin, Chun-Xiao Chen, Yun-Fei Li, Tao Cheng, Peng-Lei Jiang, Yi-Da Yang, Peng-Xu Qian, Peng-Fei Xu, Xi Jin
Yu-Wei Zhou, Wei-Xin Cheng, Lin-Ping Ding, Jian-Guo Gao, Juan Du, Chun-Xiao Chen, Xi Jin, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Yue Ren, Department of Gastroenterology, The Second Hospital of Jiaxing, Jiaxing 314000, Zhejiang Province, China
Miao-Miao Lu, Endoscopy Center, Children’s Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Ling-Ling Xu, Department of Gastroenterology, The Second People’s Hospital of Yuhang District, Hangzhou 310000, Zhejiang Province, China
Meng-Meng Zhang, Department of Gastroenterology, Hangzhou Shangcheng District People’s Hospital, Hangzhou 310003, Zhejiang Province, China
Dong Chen, Department of Colorectal Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Ci-Liang Jin, Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Yun-Fei Li, Tao Cheng, Peng-Fei Xu, Women’s Hospital and Institute of Genetics, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Peng-Lei Jiang, Peng-Xu Qian, Center of Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Yi-Da Yang, Department of Infectious Disease, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Author contributions: Jin X supervised the whole work, generated the concept, and wrote the manuscript; Zhou YW contributed to the writing-original draft, figures, tables, and literature search; Xu PF contributed to the writing-original draft, figures, and literature search; Ren Y, Lu MM, Xu LL, Zhang MM, Cheng WX, Ding LP, Chen D, Gao JG, Jin CL, Du J, Chen CX, Li YF and Cheng T contributed to the literature search; Yang YD, Jiang PL, and Qian PX contributed to the literature search and writing-review.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xi Jin, MD, PhD, Chief Physician, Department of Gastroenterology, The First Affiliated Hospital of Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou 310003, Zhejiang Province, China. jxfl007@zju.edu.cn
Received: September 27, 2023
Peer-review started: September 27, 2023
First decision: October 25, 2023
Revised: November 8, 2023
Accepted: December 27, 2023
Article in press: December 27, 2023
Published online: January 7, 2024
Processing time: 101 Days and 3.6 Hours
Abstract

Crohn’s disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Keywords: Inflammatory bowel disease; Crohn’s disease; Lymphatic system; Inside-out model; Immune cells; Zebrafish

Core Tip: The lymphatic system plays an active role in the pathogenesis, progression, and complications of certain diseases. Our review proposes an innovative concept of pan-lymphatic dysfunction and suggests Crohn’s disease (CD) as the intestinal manifestation of pan-lymphatic dysfunction using basic and clinical preliminary data, which may bring new perspectives to both the scientific study and clinical management of CD.