Proceedings of the National Academy of Sciences · 2018 · 49 citations · 32 references
Life SciencesImmunologyMicrobiologyHost-pathogen InteractionsInnate ImmunityMucosal ImmunologyCytokine BiologyGastrointestinal ImmunologyImmune Responses To InfectionInnate Immune ActivationInnate Immune ResponseMucosal ImmunityBacterial Invasion MechanismsEpithelial Innate SensingHomozygous DeletionHost Immune Response To Enteric InfectionInduced Pluripotent Stem CellsInnate Immunity PathwaysOrganoidsPhagocyte Antimicrobial Activity
Intestinal epithelial cells (IECs) play a key role in regulating immune responses and controlling infection. However, the direct role of IECs in restricting pathogens remains incompletely understood. Here, we provide evidence that IL-22 primed intestinal organoids derived from healthy human induced pluripotent stem cells (hIPSCs) to restrict Salmonella enterica serovar Typhimurium SL1344 infection. A combination of transcriptomics, bacterial invasion assays, and imaging suggests that IL-22–induced antimicrobial activity is driven by increased phagolysosomal fusion in IL-22–pretreated cells. The antimicrobial phenotype was absent in hIPSCs derived from a patient harboring a homozygous mutation in the IL10RB gene that inactivates the IL-22 receptor but was restored by genetically complementing the IL10RB deficiency. This study highlights a mechanism through which the IL-22 pathway facilitates the human intestinal epithelium to control microbial infection.
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Isolation and in vitro expansion of human colonic stem cells
Peter Jung, Toshiro Sato, Anna Merlos‐Suárez et al. · Nature Medicine · 2011 · 705 citations