Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis
| Autor: | Ryzhakov, G, West, N, Franchini, F, Clare, S, Ilott, N, Sansom, S, Bullers, S, Pearson, C, Costain, A, Vaughan-Jackson, A, Goettel, J, Ermann, J, Horwitz, B, Buti, L, Lu, X, Mukhopadhyay, S, Snapper, S, Powrie, FM |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Colon Science Primary Cell Culture Bone Marrow Cells Interleukin-23 Helicobacter Infections Mice Animals Humans lcsh:Science Bone Marrow Transplantation Mice Knockout Mice Inbred BALB C Macrophages Th1 Cells Colitis Inflammatory Bowel Diseases Interleukin-12 Mice Inbred C57BL Disease Models Animal Radiation Chimera lcsh:Q Female Helicobacter hepaticus Protein Kinases |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Ryzhakov, G, West, N R, Franchini, F, Clare, S, Ilott, N E, Sansom, S N, Bullers, S J, Pearson, C, Costain, A, Vaughan-Jackson, A, Goettel, J A, Ermann, J, Horwitz, B H, Buti, L, Lu, X, Mukhopadhyay, S, Snapper, S B & Powrie, F 2018, ' Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis ', Nature Communications, vol. 9, no. 1, 3797 . https://doi.org/10.1038/s41467-018-06085-5 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-06085-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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