6533b7d4fe1ef96bd12632d1

RESEARCH PRODUCT

Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection.

Markus KindermannManuela HefeleTamar MchedlidzeMarkus F. NeurathStefan WirtzClaudia GüntherChristoph BeckerGui-wei HeStefania VetranoSilvio DaneseSebastian FoerschMousumi MahapatroElisa Giner-ventura

subject

0301 basic medicineSalmonella typhimuriumCellular differentiationPopulationNotch signaling pathwayMice TransgenicBiologydigestive systemGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciences0302 clinical medicineIntestine SmallmedicineAnimalsHumansCell LineageProgenitor cellIntestinal Mucosaeducationlcsh:QH301-705.5Cell Proliferationeducation.field_of_studySalmonella Infections AnimalReceptors NotchCell growthCell DifferentiationEpithelial CellsFibroblastsInterleukin-33Intestinal epitheliumInterleukin-1 Receptor-Like 1 ProteinCell biologyMice Inbred C57BL030104 developmental biologymedicine.anatomical_structurelcsh:Biology (General)Organ SpecificityImmunologyPaneth cellSignal transduction030215 immunologySignal Transduction

description

SummaryThe intestinal epithelium constitutes an efficient barrier against the microbial flora. Here, we demonstrate an unexpected function of IL-33 as a regulator of epithelial barrier functions. Mice lacking IL-33 showed decreased Paneth cell numbers and lethal systemic infection in response to Salmonella typhimurium. IL-33 was produced upon microbial challenge by a distinct population of pericryptal fibroblasts neighboring the intestinal stem cell niche. IL-33 programmed the differentiation of epithelial progenitors toward secretory IEC including Paneth and goblet cells. Finally, IL-33 suppressed Notch signaling in epithelial cells and induced expression of transcription factors governing differentiation into secretory IEC. In summary, we demonstrate that gut pericryptal fibroblasts release IL-33 to translate bacterial infection into an epithelial response to promote antimicrobial defense.

yearjournalcountryeditionlanguage
2016-05-01Cell reports
10.1016/j.celrep.2016.04.049https://pubmed.ncbi.nlm.nih.gov/27184849