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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.

Original publication




Journal article


Nat Commun

Publication Date





Animals, Bone Marrow Cells, Bone Marrow Transplantation, Colitis, Colon, Disease Models, Animal, Female, Helicobacter Infections, Helicobacter hepaticus, Humans, Inflammatory Bowel Diseases, Interleukin-12, Interleukin-23, Macrophages, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Primary Cell Culture, Protein Kinases, Radiation Chimera, Th1 Cells