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

Publikation

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

Wissenschaftlicher Artikel/Review - 17.11.2020

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

Zitation

Guendel F, Hehlgans T, Waisman A, Becher B, Giannou A, Brachs S, Ebert K, Tanriver Y, Ludewig B, Mashreghi M, Kruglov A, Pfeffer K, Herold S, Ruedl C, Kofoed-Branzk M, Gronke K, Tizian C, Witkowski M, Cheng H, Heinz G, Heinrich F, Durek P, Norris P, Ware C, Diefenbach A. Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues. Immunity 2020; 53:1015-1032.e8.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Immunity 2020; 53

Veröffentlichungsdatum

17.11.2020

eISSN (Online)

1097-4180

Seiten

1015-1032.e8

Kurzbeschreibung/Zielsetzung

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.