Unknown,Transcriptomics,Genomics,Proteomics

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RNAseq of small intestinal organoids from mice treated with the cytokines IL-13 and IL-22 for 72 hours in combination with the BMP signaling inhibitor DMH1


ABSTRACT: The intestinal epithelium is our first line of defense against infections of the gut and the plasticity in cellular differentiation of the intestinal epithelium is an important part of this response. The changes in cellular composition is driven by immune cell derived cytokines. Here we use signature cytokines of different type of immune responses applied to small intestinal organoids to model how different immune responses affect intestinal epithelial development. Simplified, IL-13 represents type II immunity against infections such as parasites and IL-22 represents type III immunity against infections such as extracellular bacterial infections. 10 ng/mL of IL-13 and IL-22 was added for 72 hours after splitting. Furthermore, we have found BMP signaling to be important in regulating the cellular differentiation induced by IL-13. We therefore added added a combination treatment with the activin receptor-like kinase 2 (ALK-2) signaling inhibitor Dorsomorphin homolog 1 (DMH1) in concentration of 5 uM. We find that ALK-2 signaling is crucial for IL-13 driven Tuft cell differentiation.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Menno Oudhoff 

PROVIDER: E-MTAB-9185 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13-driven tuft cell hyperplasia.

Lindholm Håvard T HT   Parmar Naveen N   Drurey Claire C   Campillo Poveda Marta M   Vornewald Pia M PM   Ostrop Jenny J   Díez-Sanchez Alberto A   Maizels Rick M RM   Oudhoff Menno J MJ  

Science immunology 20220513 71


The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes of immune defense. The intestinal epithelium has a pivotal role in both immune initiation and effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, and IL-22. Here, we studied intestinal epithelial immune responses using organoid image analysis based on a convolutional neural network, transcriptomic analysis, and in vivo inf  ...[more]

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