Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis
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, t...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Springer Nature
2018
|
| _version_ | 1826258654732484608 |
|---|---|
| author | 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, F |
| author_facet | 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, F |
| author_sort | Ryzhakov, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:37:22Z |
| format | Journal article |
| id | oxford-uuid:0bb47ebe-43bc-4664-bae0-d703aec9e49b |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:37:22Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:0bb47ebe-43bc-4664-bae0-d703aec9e49b2022-03-26T09:30:57ZAlpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0bb47ebe-43bc-4664-bae0-d703aec9e49bSymplectic Elements at OxfordSpringer Nature2018Ryzhakov, GWest, NFranchini, FClare, SIlott, NSansom, SBullers, SPearson, CCostain, AVaughan-Jackson, AGoettel, JErmann, JHorwitz, BButi, LLu, XMukhopadhyay, SSnapper, SPowrie, FInflammatory 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. |
| spellingShingle | 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, F Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis |
| title | Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis |
| title_full | Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis |
| title_fullStr | Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis |
| title_full_unstemmed | Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis |
| title_short | Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis |
| title_sort | alpha kinase 1 controls intestinal inflammation by suppressing the il 12 th1 axis |
| work_keys_str_mv | AT ryzhakovg alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT westn alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT franchinif alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT clares alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT ilottn alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT sansoms alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT bullerss alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT pearsonc alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT costaina alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT vaughanjacksona alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT goettelj alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT ermannj alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT horwitzb alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT butil alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT lux alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT mukhopadhyays alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT snappers alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis AT powrief alphakinase1controlsintestinalinflammationbysuppressingtheil12th1axis |