Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis

Nature Communications
Grigory RyzhakovFiona Powrie

Abstract

Inflammatory bowel disease (IBD) are heterogenous disorders of the gastrointestinal tract caused by a spectrum of genetic and environmental factors. In mice, overlapping regions of chromosome 3 have been associated with susceptibility to IBD-like pathology, including a locus called Hiccs. However, the specific gene that controls disease susceptibility remains unknown. Here we identify a Hiccs locus gene, Alpk1 (encoding alpha kinase 1), as a potent regulator of intestinal inflammation. In response to infection with the commensal pathobiont Helicobacter hepaticus (Hh), Alpk1-deficient mice display exacerbated interleukin (IL)-12/IL-23 dependent colitis characterized by an enhanced Th1/interferon(IFN)-γ response. Alpk1 controls intestinal immunity via the hematopoietic system and is highly expressed by mononuclear phagocytes. In response to Hh, Alpk1-/- macrophages produce abnormally high amounts of IL-12, but not IL-23. This study demonstrates that Alpk1 promotes intestinal homoeostasis by regulating the balance of type 1/type 17 immunity following microbial challenge.

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Citations

Jun 11, 2019·Pharmaceutical Patent Analyst·Hermann Am Mucke
Jun 4, 2019·Frontiers in Immunology·Nathaniel R West
Sep 6, 2019·Helicobacter·Philippe Lehours, Richard L Ferrero
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Sep 11, 2021·Genetics, Selection, Evolution : GSE·Elaheh Rostamzadeh MahdabiMasood Asadi Fozi

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Datasets Mentioned

BETA
GM-CSF
GSE16879
50
GSE57945

Methods Mentioned

BETA
PMA
flow
flow cytometry
ELISA
RNA-Seq
biopsies
antisense oligonucleotides
in vitro transcription
genotyping
PCR

Software Mentioned

RNAScope
R
Panther
Adobe Photoshop
GSEA
DESeq2
Ensembl
Reactome
Bioconductor
Prism

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