Gonzalez Acera Miguel, Patankar Jay V, Diemand Leonard, Siegmund Britta, Neurath Markus F, Wirtz Stefan, Becker Christoph
Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
Front Med (Lausanne). 2021 May 31;8:664045. doi: 10.3389/fmed.2021.664045. eCollection 2021.
Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). The nature of the trigger causing an inflammatory reaction decides whether type 1, type 17, or type 2 immune responses, typically characterized by the respective T- helper cell subsets, come into effect. In the intestine, Type 2 responses have been linked with mucosal healing and resolution upon an immune challenge involving parasitic infections. However, type 2 cytokines are frequently elevated in certain types of IBD in particular ulcerative colitis (UC) leading to the assumption that Th2 cells might critically support the pathogenesis of UC raising the question of whether such elevated type 2 responses in IBD are beneficial or detrimental. In line with this, previous studies showed that suppression of IL-13 and other type 2 related molecules in murine models could improve the outcomes of intestinal inflammation. However, therapeutic attempts of neutralizing IL-13 in ulcerative colitis patients have yielded no benefits. Thus, a better understanding of the role of type 2 cytokines in regulating intestinal inflammation is required. Here, we took a comparative transcriptomic approach to address how Th2 responses evolve in different mouse models of colitis and human IBD datasets. Our data show that type 2 immune-related transcripts are induced in the inflamed gut of IBD patients in both Crohn's disease and UC and across widely used mouse models of IBD. Collectively our data implicate that the presence of a type 2 signature rather defines a distinct state of intestinal inflammation than a disease-specific pathomechanism.
炎性细胞因子启动并维持导致慢性炎症性疾病（如炎症性肠病，IBD）的过程的持续。引发炎症反应的触发因素的性质决定了1型、17型或2型免疫反应（通常以各自的辅助性T细胞亚群为特征）是否生效。在肠道中，2型反应与涉及寄生虫感染的免疫挑战后的粘膜愈合和炎症消退有关。然而，2型细胞因子在某些类型的IBD（特别是溃疡性结肠炎，UC）中经常升高，这导致人们认为Th2细胞可能对UC的发病机制起关键支持作用，从而引发了IBD中这种升高的2型反应是有益还是有害的问题。与此一致的是，先前的研究表明，在小鼠模型中抑制IL-13和其他2型相关分子可以改善肠道炎症的结果。然而，在溃疡性结肠炎患者中中和IL-13的治疗尝试并未产生益处。因此，需要更好地理解2型细胞因子在调节肠道炎症中的作用。在这里，我们采用了比较转录组学方法来研究Th2反应在不同的结肠炎小鼠模型和人类IBD数据集中是如何演变的。我们的数据表明，在克罗恩病和UC的IBD患者的发炎肠道中以及在广泛使用的IBD小鼠模型中，均诱导了2型免疫相关转录本。总体而言，我们的数据表明，2型特征的存在更确切地定义了肠道炎症的一种独特状态，而非一种疾病特异性的发病机制。
