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Transforming Growth Factor and Intestinal Inflammation: The Role of Nutrition

机译:转化生长因子和肠炎:营养的作用

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The intestinal mucosa possesses a complex epithelial barrier and a well-organized local immune system, which both efficiently protect this internal-external surface against potential microbial aggressions while guaranteeing tolerance towards harmless bacteria or antigens (oral tolerance). There is good experimental evidence that the intestinal micro-biota is a main driver for the development of the mucosal immune system. Any perturbations/changes of this interaction with the intestinal microbiota or the microbial colonization process may cause health problems with short- and eventually long-term consequences, such as suspected for allergic or dysimmune disorders. Dendritic cells (DC) play a key role in the initiation of immune responses. Immune responses elicited by intestinal DC differ markedly from those initiated by spleen-derived DC: while intestinal DC induce anti-inflammatory and tolerogenic responses to harmless antigens such as derived from the resident microflora or harmless food allergens, systemic immune activation yields in a strong inflammatory TH1/TH17 reaction to the same antigens. The recent discovery how DC functions are regulated and imprinted by the microenvironment (DC conditioning) will be discussed in this review. High concentrations of retinoic acid or vitamin D metabolites, thymic stromal lymphopoietin and/or transforming growth factor-beta (TGF-beta) activate signaling programs in DC that yield in priming of regulatory and anti-inflammatory T cell responses. TGF-beta is one of the key factors implicated in intestinal immune regulation; it is produced by a large variety of cells in the intestinal mucosa, including intestinal epithelial cells, lymphocytesandmonocytes/macrophages/DC. An important anti-inflammatory effect of TGF-p on the immune system is the promotion and generation of FOXP3-positive regulatory T cells in the intestinal compartment. There are first and encouraging data from the treatment of Crohn's disease, an inflammatory Gl condition, that targeted enteral therapy with optimized concentrations of immunoregulatory peptides, such as TGF-beta, might of interest for the treatment of inflammatory disorders.
机译:肠粘膜具有复杂的上皮屏障和良好组织的局部免疫系统,其既有效保护这种内外表面,以防止潜在的微生物侵蚀,同时保证对无害细菌或抗原(口服耐受性)的耐受性。存在良好的实验证据,即肠道微型生物生物是用于粘膜免疫系统发展的主要驱动因素。任何与肠道微生物群或微生物结肠化过程相互作用的扰动/变化可能导致健康问题短期和最终的长期后果,例如怀疑过敏性或疑似症状疾病。树突细胞(DC)在引发免疫反应中起关键作用。由肠DC引发的免疫应答显着不同于由脾脏衍生的DC引发的反应:而肠道直流诱导抗炎和耐受性对无害抗原的反应,例如来自驻留的微生物或无害食物过敏原,系统免疫活化产量在强烈的炎症中Th1 / th17对同一抗原的反应。最近发现DC功能如何受到微环境(DC条件)的监管和印制,将在本次审查中讨论。高浓度的视黄酸或维生素D代谢物,胸腺基质淋巴结素和/或转化生长因子-β(TGF-BETA)在DC中激活信号通信程序,其促进调节和抗炎性T细胞应答的灌注。 TGF-β是涉及肠免疫调节的关键因素之一;它由肠粘膜中的各种细胞产生,包括肠上皮细胞,淋巴细胞和甘蔗细胞/巨噬细胞/ DC。 TGF-P对免疫系统的重要抗炎作用是肠道中促进和产生Foxp3阳性调节T细胞。首先和令人鼓舞的数据来自治疗克罗恩病,炎症GL病症,靶向肠道疗法,具有优化浓度的免疫调节肽,例如TGF-β,可能感兴趣的炎症性疾病。

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