Intestinal dendritic cells, gatekeepers preventing ethanol-induced liver disease.
Intestinal dendritic cells, gatekeepers preventing ethanol-induced liver disease.
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肠道树突状细胞，预防乙醇引起的肝病的看门人。
DOI：
10.1097/hep.0000000000000236
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Liangpunsakul,Suthat
中科院分区：
文献类型：
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作者：
Llorente,Cristina;Rungratanawanich,Wiramon;Liangpunsakul,Suthat
酒精相关性肝病（ALD）是一种全球性疾病，具有高发病率和高死亡率，占全球所有死亡的5.3%。除了戒酒之外，缺乏其他治疗方法，这证明了在该领域进行研究的必要性。[1]必须确定新的有效治疗沿着ALD发病机制，以减轻这种毁灭性疾病的全球负担。肠道和肝脏之间的微妙相互作用在ALD的病理生理学中至关重要。乙醇滥用会突然破坏保护肠道-肝脏平衡的成分。乙醇促进肠道生态失调，小肠细菌过度生长，肠道通透性和微生物易位到循环和肝脏，从而引发炎症并使ALD恶化。[2]了解这一复杂方程的关键因素对于ALD的预防和治疗至关重要。宿主肠道免疫系统影响肠道微生物群的丰度和组成，并参与肠-肝轴的调节。了解ALD发病机制中肠道免疫系统的影响和机制途径是相关的，因为它可能导致靶向治疗的鉴定。树突状细胞（Dendritic cells，DC）是来源于单核-巨噬细胞DC前体的骨髓源性抗原呈递细胞。肠DC存在于有组织的淋巴组织如派伊尔淋巴结、肠系膜淋巴结和固有层（LP）中。DC耐受抗原和肠道共生体，同时制定适应性免疫反应以对抗病原体。在LP中，髓样DC可分为2个不同的亚群：浆细胞样DC和常规DC（cDC）。肠道中的CDCs可分为CD103 + CD11b − cDC 1、CD103 + CD11b+和CD103 − CD11b + cDC 2亚群。[3]这些常规DC亚群的发育受不同转录因子的调控。cDC 1发育由碱性亮氨酸拉链转录因子ATF-4样3（BATF3）和干扰素调节因子8（IRF8）定义，
Alcohol-associated liver disease (ALD) is a global illness with high morbidity and mortality, accounting for 5.3% of all deaths worldwide. The lack of treatments other than alcohol abstinence evidences the necessity of research in the field.[1] Novel effective therapies along with the mechanism of ALD pathogenesis must be determined to mitigate the global burden of this devastating disease. A delicate interplay between the gut and liver is crucial in the pathophysiology of ALD. Ethanol misuse abruptly disrupts the components shielding the gut-liver balance. Ethanol promotes gut dysbiosis, small intestinal bacterial overgrowth, intestinal permeability, and microbial translocation to the circulation and liver, which triggers inflammation and aggravates ALD.[2] Understanding the critical factors of this complex equation is essential for ALD prevention and therapy.The host intestinal immune system influences the intestinal microbiota abundance and composition and participates in the regulation of the gut-liver axis. Understanding the implications and mechanistic pathways of the intestinal immune system in ALD pathogenesis is of relevance, as it may lead to the identification of targeted therapies. Dendritic cells (DCs) are bone marrow–originated antigen presenting cells derived from monocyte-macrophages DC precursors. Intestinal DCs are found within organized lymphoid tissue such as Peyer’s patches, mesenteric lymph nodes, and in the lamina propria (LP). DCs tolerate antigens and gut symbionts while strategizing adaptive immune responses to combat pathogens. In the LP, myeloid DCs can be classified into 2 different subsets: plasmacytoid DCs and conventional DCs (cDCs). CDCs in the gut can be subdivided into the CD103+ CD11b− cDC1, and the CD103+ CD11b+ and CD103− CD11b+ cDC2 subsets.[3] The development of these conventional DCs subsets is under the regulation of distinct transcription factors. cDC1 development is defined by basic leucine zipper transcription factor ATF-4 like 3 (BATF3) and interferon regulatory factor 8 (IRF8),