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Interleukin\u201035 (IL\u201035), as a cytokine with immunomodulatory function, has been shown to have therapeutic effects on UC, but its mechanism is not yet clear. Therefore, we constructed Pichia pastoris stably expressing IL\u201035 which enables the cytokines to reach the diseased mucosa, and explored whether upregulation of T\u2010cell protein tyrosine phosphatase (TCPTP) in macrophages is involved in the mechanisms of IL\u201035\u2010mediated attenuation of UC. After the successful construction of engineered bacteria expressing IL\u201035, a colitis model was successfully induced by giving BALB\/c mice a solution containing 3% dextran sulfate sodium (DSS). Mice were treated with Pichia\/IL\u201035, empty plasmid\u2010transformed Pichia (Pichia\/0), or PBS by gavage, respectively. The expression of TCPTP in macrophages (RAW264.7, BMDMs) and intestinal tissues after IL\u201035 treatment was detected. After administration of Pichia\/IL\u201035, the mice showed significant improvement in weight loss, bloody stools, and shortened colon. Colon pathology also showed that the inflammatory condition of mice in the Pichia\/IL\u201035 treatment group was alleviated. Notably, Pichia\/IL\u201035 treatment not only increases local M2 macrophages but also decreases the expression of inflammatory cytokine IL\u20106 in the colon. With Pichia\/IL\u201035 treatment, the proportion of M1 macrophages, Th17, and Th1 cells in mouse MLNs were markedly decreased, while Tregs were significantly increased. <jats:italic>In vitro<\/jats:italic> experiments, IL\u201035 significantly promoted the expression of TCPTP in macrophages stimulated with LPS. Similarly, the mice in the Pichia\/IL\u201035 group also expressed more TCPTP than that of the untreated group and the Pichia\/0 group.<\/jats:p>","DOI":"10.1155\/2024\/3282679","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T09:19:25Z","timestamp":1718270365000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Upregulation of TCPTP in Macrophages Is Involved in IL\u201035 Mediated Attenuation of Experimental Colitis"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2661-2173","authenticated-orcid":false,"given":"Baoren","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of General Surgery Tianjin Medical University General Hospital  Tianjin China  tjmugh.com.cn"},{"name":"Tianjin General Surgery Institute  Tianjin 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