{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:11:12Z","timestamp":1793045472081,"version":"4.5.0"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The gastrointestinal tract, a vital immune organ in the human body, serves as the primary site of direct contact with external antigens. Maintaining immune tolerance is essential for preventing the onset and progression of digestive system diseases. Autoimmune diseases and tumors represent the overactivation and evasion of the immune system, respectively, and the imbalance of \u201cimmune tolerance\u201d is the common core mechanism underlying both conditions. The function of traditional Chinese medicine in regulating the immune function of the digestive system has attracted wide attention, especially in the dual regulation of immune tolerance.\n                    <jats:italic>Astragalus membranaceus<\/jats:italic>\n                    and its derivatives exhibit remarkable efficacy in restoring immune tolerance. Mechanistically, these agents exert multi-target regulatory effects via modulating core signaling pathways, remodeling immune cell function and gut microbiota composition. Concurrently, they rebalance pivotal immune axes, such as Th1\/Th2 and Treg\/Th17, thereby systematically reinstating immune homeostasis rather than exerting isolated, unilateral modulations. This review systematically summarizes 112 studies published in PubMed, Web of Science and CNKI from December 2020 to December 2025, focusing on the immunomodulatory mechanisms and evidence of\n                    <jats:italic>Astragalus membranaceus<\/jats:italic>\n                    and its derivatives in the treatment of digestive diseases. It further examines the limitations of current studies and potential future research directions, thereby offering a theoretical basis for the development of novel drugs derived from\n                    <jats:italic>Astragalus membranaceus<\/jats:italic>\n                    and its active compounds.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1855390","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:51:42Z","timestamp":1781671902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of Astragalus membranaceus and its derivatives in digestive system diseases: reconstruction of immune tolerance"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyue","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Xi\u2019an Central Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xi\u2019an Central Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xi\u2019an Central Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xi\u2019an Central Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xi\u2019an Central Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xi\u2019an Central Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00970-x","article-title":"Therapeutic induction of antigen-specific immune tolerance","volume":"24","author":"Kenison","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5503","DOI":"10.3390\/ijms26125503","article-title":"Understanding the immune system's intricate balance: Activation, tolerance, and self-protection","volume":"26","author":"Chen","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2022.103141","article-title":"Extrathymic AIRE-expressing cells: Friends or foes in autoimmunity and cancer","volume":"21","author":"van Laar","year":"2022","journal-title":"Autoimmun Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1206720","article-title":"Immune response and treatment targets of chronic hepatitis B virus infection: innate and adaptive immunity","volume":"13","author":"Zheng","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1088129","article-title":"Yin and yang roles of B lymphocytes in solid tumors: Balance between antitumor immunity and immune tolerance\/immunosuppression in tumor-draining lymph nodes","volume":"13","author":"Katakai","year":"2023","journal-title":"Front Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.023671","article-title":"Modulating the intestinal immune system: the role of lymphotoxin and GALT organs","volume":"53","author":"Spahn","year":"2004","journal-title":"Gut"},{"key":"B7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/35095573","article-title":"Man the barrier! 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