title: Interleukin‑21 promotes the development of ulcerative colitis and regulates the proliferation and secretion of follicular T helper cells in the colitides microenvironment.
abstract: Patients with ulcerative colitis (UC) are at increased risk of developing colitis‑associated colon cancer. Previous studies have indicated that interleukin (IL)‑21, which is predominantly secreted by follicular T helper (Tfh) cells, is overproduced in inflammatory bowel diseases. In order to investigate the role of IL‑21 in UC and the association between IL‑21 and Tfh cells, the number of Tfh cells and the level of IL‑21 were investigated in colonic tissues from UC patients and wild‑type (WT) mice, which were induced by dextran sulphate sodium (DSS). High Tfh cell counts and levels of IL‑21 were observed in UC patients and WT mice with DSS‑induced colitis. Subsequent comparison of the mucosal damage and expression of Tfh‑associated cytokines in the WT mice and IL‑21 knockout (IL‑21KO) mice following DSS administration, revealed that IL‑21KO mice were largely protected against colitis and exhibited reduced infiltration of Tfh cells, as well as decreased production of Tfh‑associated cytokines. The present study also found that IL‑21 was necessary for the proliferation and secretion of Tfh cells in vitro. In addition, neutralization of IL‑21 in DSS‑administered WT mice using anti‑IL‑21 reduced the number of Tfh cells and the level of mucosal damage. Administration of a neutralizing IL‑21 antibody decreased the colonic infiltration of Tfh cells and reduced damage to the mucosa. These results indicated that Tfh cells are important in UC and that its effector molecule, IL‑21, is not only a critical regulator of inflammation, but also regulates the proliferation and response of Tfh cells in the colitis microenvironment.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Songbing
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Gastrointestinal Surgery, The First People's Hospital of Wujiang City, Wujiang Hospital Afﬁliated to Nantong University, Wujiang, Jiangsu 215200, P.R. China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: You
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D057134:Antibodies, Neutralizing; C513179:CXCR5 protein, mouse; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D023201:CD40 Ligand; D016264:Dextran Sulfate; D000098546:Interleukin-21