6533b82afe1ef96bd128b847

RESEARCH PRODUCT

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

Susanne HeroldSebastian BrachsPaula S. NorrisAndrey KruglovKonrad GronkeAnastasios D. GiannouBurkhard BecherFabian GuendelCarl F. WareYakup TanriverBurkhard LudewigChristiane RuedlMir-farzin MashreghiHung-wei ChengGitta Anne HeinzKarolina EbertCaroline TizianKlaus PfefferMario WitkowskiPawel DurekThomas HehlgansAndreas DiefenbachMichael Kofoed-branzkAri WaismanFrederik Heinrich

subject

0301 basic medicineImmunologyPopulationCD11cGene ExpressionMice TransgenicC-C chemokine receptor type 6BiologyFlow cytometryImmunophenotyping03 medical and health sciencesMicePeyer's Patches0302 clinical medicineRNA Small CytoplasmicmedicineImmunology and AllergyAnimalsIntestinal Mucosaeducationeducation.field_of_studymedicine.diagnostic_testGene Expression ProfilingInnate lymphoid cellInterleukinDendritic CellsReceptors InterleukinLipid MetabolismImmunity InnateLymphocyte SubsetsCell biology030104 developmental biologyInfectious DiseasesLymphotoxinGene Expression Regulation030220 oncology & carcinogenesisHomeostasisBiomarkersSignal Transduction

description

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.

yearjournalcountryeditionlanguage
2019-06-12Immunity
10.1016/j.immuni.2020.10.012https://pubmed.ncbi.nlm.nih.gov/33207209