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

被引：53

作者：

Guendel, Fabian ^{[1
,2
,3
]}

Kofoed-Branzk, Michael ^{[1
,2
,3
]}

Gronke, Konrad ^{[1
,2
,3
]}

Tizian, Caroline ^{[1
,2
,3
]}

Witkowski, Mario ^{[1
,2
,3
]}

Cheng, Hung-Wei ^{[4
]}

Heinz, Gitta Anne ^{[5
]}

Heinrich, Frederik ^{[5
]}

Durek, Pawel ^{[5
]}

Norris, Paula S. ^{[7
]}

Ware, Carl F. ^{[7
]}

Ruedl, Christiane ^{[8
]}

Herold, Susanne ^{[9
]}

Pfeffer, Klaus ^{[10
]}

Hehlgans, Thomas ^{[11
,12
]}

Waisman, Ari ^{[13
]}

Becher, Burkhard ^{[14
]}

Giannou, Anastasios D. ^{[15
,16
]}

Brachs, Sebastian ^{[17
,18
,19
]}

Ebert, Karolina ^{[20
]}

Tanriver, Yakup ^{[20
,21
]}

Ludewig, Burkhard ^{[4
,14
]}

Mashreghi, Mir-Farzin ^{[5
,6
]}

Kruglov, Andrey A. ^{[22
,23
,24
,25
]}

Diefenbach, Andreas ^{[1
,2
,3
]}

机构：

[1] Charite Univ Med Berlin, Dept Microbiol Infect Dis & Immunol, Lab Innate Immun, Campus Benjamin Franklin,Hindenburgdamm 30, D-12203 Berlin, Germany

[2] Berlin Inst Hlth BIH, Anna Louisa Karsch Str 2, D-10117 Berlin, Germany

[3] Deutsch Rheuma Forschungszentrum DRFZ, Mucosal & Dev Immunol, D-10117 Berlin, Germany

[4] Kantonsspital St Gallen, Inst Immunobiol, St Gallen, Switzerland

[5] Deutsch Rheuma Forschungszentrum DRFZ, Therapeut Gene Regulat, D-10117 Berlin, Germany

[6] Charite Univ Med Berlin, BIH Ctr Regenerat Therapies BCRT, Berlin, Germany

[7] Sanford Burnham Prebys Med Discovery Inst, Lab Mol Immunol, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA

[8] Nanyang Technol Univ Singapore, Sch Biol Sci, Singapore, Singapore

[9] Univ Giessen & Marburg Lung Ctr, Dept Internal Med 2, German Ctr Lung Res DZL, Giessen, Germany

[10] Heinrich Heine Univ Dusseldorf, Inst Med Microbiol & Hosp Hyg, Dusseldorf, Germany

[11] Regensburg Ctr Intervent Immunol RCI, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany

[12] Regensburg Univ, Chair Immunol, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany

[13] Johannes Gutenberg Univ Mainz, Inst Mol Med, Univ Med Ctr, Mainz, Germany

[14] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland

[15] Univ Med Ctr Hamburg Eppendorf, Dept Med, Sect Mol Immunol & Gastroenterol, D-20246 Hamburg, Germany

[16] Univ Med Ctr Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, D-20246 Hamburg, Germany

[17] Charite Univ Med Berlin, Dept Endocrinol & Metab, Charitepl 1, D-10117 Berlin, Germany

[18] DZHK German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany

[19] Charite Univ Med Berlin, Ctr Cardiovasc Res CCR, Hessische Str 3-4, D-10115 Berlin, Germany

[20] Univ Freiburg, Fac Med, Inst Med Microbiol & Hyg, Freiburg, Germany

[21] Univ Freiburg, Med Ctr Univ Freiburg, Fac Med, Dept Internal Med 4, Freiburg, Germany

[22] Deutsch Rheuma Forschungszentrum DRFZ, Microbiota & Chron Inflammat, D-10117 Berlin, Germany

[23] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119234, Russia

[24] Moscow MV Lomonosov State Univ, Biol Fac, Moscow 119234, Russia

[25] Russian Acad Sci, Ctr Precis Genome Editing & Genet Technol Biomed, Engelhardt Inst Mol Biol, Moscow 119991, Russia

来源：

IMMUNITY | 2020年 / 53卷 / 05期

基金：

欧洲研究理事会; 瑞士国家科学基金会;

关键词：

ROR-GAMMA-T; GREEN FLUORESCENT PROTEIN; SIGNALING CONTROLS; INDUCER CELLS; RECEPTOR; LYMPHOTOXIN; EXPRESSION; IL-22; MICE; MACROPHAGES;

D O I：

10.1016/j.immuni.2020.10.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-beta 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.

引用

页码：1015 / +

页数：26

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