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Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues
Immunity ( IF 32.4 ) Pub Date : 2020-11-17 , DOI: 10.1016/j.immuni.2020.10.012
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

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



中文翻译:

第3组先天淋巴样细胞对IL-22BP产生的树突状细胞的不同亚组进行编程,将其定性为孤立的肠淋巴组织。

孤肠淋巴组织(例如隐斑(CP)和孤立的淋巴滤泡(ILF))构成稳态激活集线器,其中包含连续产生白介素(IL)-22的第3组先天性淋巴样细胞(ILC3)。CPs和ILFs的外表面由CD11c +细胞特征不清晰的区域划分。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,我们发现CP和ILF相关的CD11c +细胞是肠道cDC的转录独特子集,我们将其称为CIA-DC。CIA-DC需要由CP和ILF驻留的CCR6 +进行编程IDC3通过cDC中的淋巴毒素-β受体信号传导。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衍生的IL-22BP的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。我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识。

更新日期:2020-11-17
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