研究揭示免疫檢查點控制營養吸收的機制
作者：
小柯機器人發布時間：2020/11/19 13:10:35
德國柏林慈善大學Andreas Diefenbach研究團隊取得一項新突破。他們提出第3組先天性淋巴樣細胞（ILC3）對白介素（IL）-22BP產生的樹突狀細胞的不同亞組進行編程，將其定性為單獨的腸淋巴組織。相關論文於2020年11月17日發表於《免疫》。
使用腸道單核吞噬細胞的全基因組單細胞轉錄譜分析和多維流式細胞術，他們發現隱斑（CP）和孤立的淋巴濾泡（ILF）相關的CD11c +細胞是腸道cDC的轉錄特異亞群，他們將其稱為CIA-DC。 CIA-DCs需要通過cDCs中的淋巴毒素β受體信號傳導，由CP和ILF駐留的CCR6 + ILC3進行編程。CIA-DCs差異表達與免疫調節相關的基因，並且是穩定狀態下IL-22結合蛋白（IL-22BP）的主要細胞來源。缺乏CIA-DC來源的IL-22BP小鼠表現出上皮脂質轉運蛋白的表達減少，脂質吸收減少以及體內脂肪穩態的變化。他們的發現為控制營養吸收的免疫調節檢查點的設計原理提供了見解。
據悉，孤腸淋巴組織（例如CP和ILF）構成穩態激活集線器，其中包含連續產生IL-22的ILC3。CPs和ILFs的外表面由CD11c +細胞特徵不清晰的區域劃分。
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