Lipidated IL-22 Alone or Combined with Immunomodulatory Agents Improves Disease Endpoints and Promotes Mucosal Healing in a Mouse Model of Chronic Dextran Sodium Sulfate-Induced Colitis.
Sidsel Støy, Silvia D'Alessio, Thomas Damgaard Sandahl, Anders Dige, Anne Louise Kjølbye, Rasmus Jorgensen, Silvio Danese, Martijn van de Bunt
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引用次数: 0
Abstract
Background: IL-22 facilitates mucosal healing by directly inducing epithelial regeneration and barrier integrity, which is essential for achieving remission and thereby treating inflammatory bowel disease.
Aims: Here, we evaluated efficacy of a novel lipidated IL-22 alone and in combination with immunomodulatory agents in addressing chronic dextran sodium sulfate (DSS)-induced colitis in mice and demonstrated action of IL-22 on mucosal healing.
Methods: Mice were treated with DSS, followed by various doses of lipidated IL-22, anti-TNF antibody, fingolimod, or anti-mouse α4β7 integrin antibody. Additionally, gene expression was determined in colonic biopsies from ulcerative colitis patients to assess effects of IL-22 stimulation.
Results: Lipidated IL-22 significantly improved all aspects of chronic DSS-induced colitis in mice, with dose-dependent efficacy. Combinations of a range of immunomodulatory agents with lipidated IL-22 showed further additive reductions in disease activity, significantly greater than those of monotherapies. Immunohistochemistry revealed that lipidated IL-22 increased epithelial cell proliferation and reduced CD3+ T-cell infiltration, indicating enhanced mucosal healing. This was further supported gene expression data from colonic biopsies from ulcerative colitis patients after IL-22 stimulation.
Conclusions: Given the challenges in achieving long-term remission in IBD due to inflammation and mucosal damage, lipidated IL-22 presents a promising treatment option that directly promotes mucosal healing, unlike traditional immunomodulatory therapies.
期刊介绍：
Digestive Diseases and Sciences publishes high-quality, peer-reviewed, original papers addressing aspects of basic/translational and clinical research in gastroenterology, hepatology, and related fields. This well-illustrated journal features comprehensive coverage of basic pathophysiology, new technological advances, and clinical breakthroughs; insights from prominent academicians and practitioners concerning new scientific developments and practical medical issues; and discussions focusing on the latest changes in local and worldwide social, economic, and governmental policies that affect the delivery of care within the disciplines of gastroenterology and hepatology.
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