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Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Acute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of <jats:italic>Tlr2 in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The numbers of anti-inflammatory response-related cells, such as M2 macrophages (<jats:italic>P<\/jats:italic> = 3.2 \u00d7 10<jats:sup>\u20133<\/jats:sup>), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (<jats:italic>P<\/jats:italic> = 3.0 \u00d7 10<jats:sup>\u20138<\/jats:sup>), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8\/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, <jats:italic>TLR2<\/jats:italic>might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2022.1052466","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T07:46:25Z","timestamp":1671003985000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Identification of novel immune-related targets mediating disease progression in acute pancreatitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Qiang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongchao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianpeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sile","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1080\/13651820701713766","article-title":"Acute pancreatitis\u2013from cellular signalling to complicated clinical course","volume":"9","author":"Andersson","year":"2007","journal-title":"HPB (Oxford)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1007\/s00011-011-0370-1","article-title":"TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate","volume":"60","author":"Awla","year":"2011","journal-title":"Inflammation Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/path.1491","article-title":"Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome","volume":"202","author":"Bhatia","year":"2004","journal-title":"J. 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