Cryptopatches are essential for the development of human GALT.

Cryptopatches are essential for the development of human GALT.
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Cryptopatches对于人类Galt的发展至关重要。

DOI:
10.1016/j.celrep.2013.05.037
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发表时间:
2013-06-27
期刊:
影响因子:
8.8
通讯作者:
Garcia JV
Garcia JV
中科院分区:
生物学1区
文献类型:
--
作者:
Nochi T;Denton PW;Wahl A;Garcia JV

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人类肠道相关淋巴组织(GALT)异常与感染性和自身免疫性疾病有关,这些疾病会导致胃肠道(GI)免疫系统功能障碍。为了帮助在体内研究GALT病理,我们生物工程的人-小鼠嵌合模型,其特征在于起源于小鼠cryptopatches的人GALT结构的发展。这一新的观察结果代表了我们对密码锁在人类GALT发生中的作用的机制理解的根本性突破,并强调了人类和小鼠之间这一发育过程的进化保守性。在这些GALT结构中发生向伊加的免疫球蛋白类转换,导致在整个肠固有层中产生许多人IgA产生浆细胞。GALT结构内的CD 4 + T细胞耗竭由HIV感染引起,如在人类中。这种人-小鼠嵌合模型代表了目前可用于研究的最全面的实验平台,以及旨在修复疾病损伤的GALT的治疗剂的临床前疗效测试。
Abnormal gut-associated lymphoid tissue (GALT) in humans is associated with infectious and autoimmune diseases, which cause dysfunction of the gastrointestinal (GI) tract immune system. To aid in investigating GALT pathologies in vivo, we bioengineered a human-mouse chimeric model characterized by the development of human GALT structures originating in mouse cryptopatches. This novel observation represents a fundamental breakthrough in our mechanistic understanding of the role of cryptopatches in human GALT genesis and emphasizesthe evolutionary conservation of this developmental process between humans and mice. Immunoglobulin class switching to IgA occurs in these GALT structures leading to numerous human IgA-producing plasma cells throughout the intestinal lamina propria. CD4+ T cell depletion within GALT structures results from HIV infection, as in humans. This human-mouse chimeric model represents the most comprehensive experimental platform currently available for the study and the pre-clinical efficacy testing of therapeutics designed to repair disease-damaged GALT.
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