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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.

Original publication

DOI

10.1073/pnas.1811866115

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

02/10/2018

Volume

115

Pages

10118 - 10123

Keywords

Salmonella, interleukin-22, intestinal organoids, Epithelial Cells, Humans, Induced Pluripotent Stem Cells, Interleukin-10 Receptor beta Subunit, Interleukin-21 Receptor alpha Subunit, Interleukins, Intestinal Mucosa, Phagosomes, Salmonella Infections, Salmonella typhimurium