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研究揭示免疫检查点控制营养吸收的机制
作者:小柯机器人 发布时间:2020/11/19 13:10:35

德国柏林慈善大学Andreas Diefenbach研究团队取得一项新突破。他们提出第3组先天性淋巴样细胞(ILC3)对白介素(IL)-22BP产生的树突状细胞的不同亚组进行编程,将其定性为单独的肠淋巴组织。相关论文于2020年11月17日发表于《免疫》。

使用肠道单核吞噬细胞的全基因组单细胞转录谱分析和多维流式细胞术,他们发现隐斑(CP)和孤立的淋巴滤泡(ILF)相关的CD11c +细胞是肠道cDC的转录特异亚群,他们将其称为CIA-DC。 CIA-DCs需要通过cDCs中的淋巴毒素β受体信号传导,由CP和ILF驻留的CCR6 + ILC3进行编程。CIA-DCs差异表达与免疫调节相关的基因,并且是稳定状态下IL-22结合蛋白(IL-22BP)的主要细胞来源。缺乏CIA-DC来源的IL-22BP小鼠表现出上皮脂质转运蛋白的表达减少,脂质吸收减少以及体内脂肪稳态的变化。他们的发现为控制营养吸收的免疫调节检查点的设计原理提供了见解。

据悉,孤肠淋巴组织(例如CP和ILF)构成稳态激活集线器,其中包含连续产生IL-22的ILC3。CPs和ILFs的外表面由CD11c +细胞特征不清晰的区域划分。

附:英文原文

Title: Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues

Author: Fabian Guendel, Michael Kofoed-Branzk, Konrad Gronke, Caroline Tizian, Mario Witkowski, Hung-Wei Cheng, Gitta Anne Heinz, Frederik Heinrich, Pawel Durek, Paula S. Norris, Carl F. Ware, Christiane Ruedl, Susanne Herold, Klaus Pfeffer, Thomas Hehlgans, Ari Waisman, Burkhard Becher, Anastasios D. Giannou, Sebastian Brachs, Karolina Ebert, Yakup Tanriver, Burkhard Ludewig, Mir-Farzin Mashreghi, Andrey A. Kruglov, Andreas Diefenbach

Issue&Volume: 2020/11/17

Abstract: Solitary intestinal lymphoid tissues such as cryptopatches (CPs) and isolated lymphoidfollicles (ILFs) constitute steady-state activation hubs containing group 3 innatelymphoid cells (ILC3) that continuously produce interleukin (IL)-22. The outer surfaceof CPs and ILFs is demarcated by a poorly characterized population of CD11c+ cells. Using genome-wide single-cell transcriptional profiling of intestinal mononuclearphagocytes and multidimensional flow cytometry, we found that CP- and ILF-associatedCD11c+ cells were a transcriptionally distinct subset of intestinal cDCs, which we termCIA-DCs. CIA-DCs required programming by CP- and ILF-resident CCR6+ ILC3 via lymphotoxin-β receptor signaling in cDCs. CIA-DCs differentially expressedgenes associated with immunoregulation and were the major cellular source of IL-22binding protein (IL-22BP) at steady state. Mice lacking CIA-DC-derived IL-22BP exhibiteddiminished expression of epithelial lipid transporters, reduced lipid resorption,and changes in body fat homeostasis. Our findings provide insight into the designprinciples of an immunoregulatory checkpoint controlling nutrient absorption.

DOI: 10.1016/j.immuni.2020.10.012

Source:https://www.cell.com/immunity/fulltext/S1074-7613(20)30453-2

 

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx