TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα
Abstract Background Human aging is characterized by a state of chronic inflammation, termed inflammaging, for which the causes are incompletely understood. It is known, however, that macrophages play a driving role in establishing inflammaging by promoting pro-inflammatory rather than anti-inflammat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Immunity & Ageing |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12979-023-00350-y |
| _version_ | 1797784420596318208 |
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| author | Alexandre Poirier Chenyue Wu Ana Maria Hincapie Zuzet Martinez-Cordova Belma Melda Abidin Michel L. Tremblay |
| author_facet | Alexandre Poirier Chenyue Wu Ana Maria Hincapie Zuzet Martinez-Cordova Belma Melda Abidin Michel L. Tremblay |
| author_sort | Alexandre Poirier |
| collection | DOAJ |
| description | Abstract Background Human aging is characterized by a state of chronic inflammation, termed inflammaging, for which the causes are incompletely understood. It is known, however, that macrophages play a driving role in establishing inflammaging by promoting pro-inflammatory rather than anti-inflammatory responses. Numerous genetic and environmental risk factors have been implicated with inflammaging, most of which are directly linked to pro-inflammatory mediators IL-6, IL1Ra, and TNFα. Genes involved in the signaling and production of those molecules have also been highlighted as essential contributors. TAOK3 is a serine/threonine kinase of the STE-20 kinase family that has been associated with an increased risk of developing auto-immune conditions in several genome-wide association studies (GWAS). Yet, the functional role of TAOK3 in inflammation has remained unexplored. Results We found that mice deficient in the serine/Threonine kinase Taok3 developed severe inflammatory disorders with age, which was more pronounced in female animals. Further analyses revealed a drastic shift from lymphoid to myeloid cells in the spleens of those aged mice. This shift was accompanied by hematopoietic progenitor cells skewing in Taok3−/− mice that favored myeloid lineage commitment. Finally, we identified that the kinase activity of the enzyme plays a vital role in limiting the establishment of proinflammatory responses in macrophages. Conclusions Essentially, Taok3 deficiency promotes the accumulation of monocytes in the periphery and their adoption of a pro-inflammatory phenotype. These findings illustrate the role of Taok3 in age-related inflammation and highlight the importance of genetic risk factors in this condition. |
| first_indexed | 2024-03-13T00:39:38Z |
| format | Article |
| id | doaj.art-656770022ec9402d93d049a40aef9c57 |
| institution | Directory Open Access Journal |
| issn | 1742-4933 |
| language | English |
| last_indexed | 2024-03-13T00:39:38Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Immunity & Ageing |
| spelling | doaj.art-656770022ec9402d93d049a40aef9c572023-07-09T11:25:02ZengBMCImmunity & Ageing1742-49332023-07-0120111210.1186/s12979-023-00350-yTAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFαAlexandre Poirier0Chenyue Wu1Ana Maria Hincapie2Zuzet Martinez-Cordova3Belma Melda Abidin4Michel L. Tremblay5Rosalind and Morris Goodman Cancer Institute, McGill UniversityRosalind and Morris Goodman Cancer Institute, McGill UniversityRosalind and Morris Goodman Cancer Institute, McGill UniversityRosalind and Morris Goodman Cancer Institute, McGill UniversityRosalind and Morris Goodman Cancer Institute, McGill UniversityRosalind and Morris Goodman Cancer Institute, McGill UniversityAbstract Background Human aging is characterized by a state of chronic inflammation, termed inflammaging, for which the causes are incompletely understood. It is known, however, that macrophages play a driving role in establishing inflammaging by promoting pro-inflammatory rather than anti-inflammatory responses. Numerous genetic and environmental risk factors have been implicated with inflammaging, most of which are directly linked to pro-inflammatory mediators IL-6, IL1Ra, and TNFα. Genes involved in the signaling and production of those molecules have also been highlighted as essential contributors. TAOK3 is a serine/threonine kinase of the STE-20 kinase family that has been associated with an increased risk of developing auto-immune conditions in several genome-wide association studies (GWAS). Yet, the functional role of TAOK3 in inflammation has remained unexplored. Results We found that mice deficient in the serine/Threonine kinase Taok3 developed severe inflammatory disorders with age, which was more pronounced in female animals. Further analyses revealed a drastic shift from lymphoid to myeloid cells in the spleens of those aged mice. This shift was accompanied by hematopoietic progenitor cells skewing in Taok3−/− mice that favored myeloid lineage commitment. Finally, we identified that the kinase activity of the enzyme plays a vital role in limiting the establishment of proinflammatory responses in macrophages. Conclusions Essentially, Taok3 deficiency promotes the accumulation of monocytes in the periphery and their adoption of a pro-inflammatory phenotype. These findings illustrate the role of Taok3 in age-related inflammation and highlight the importance of genetic risk factors in this condition.https://doi.org/10.1186/s12979-023-00350-yInflammagingMacrophagesTAOK3Pro-inflammatory cytokinesChemotaxis |
| spellingShingle | Alexandre Poirier Chenyue Wu Ana Maria Hincapie Zuzet Martinez-Cordova Belma Melda Abidin Michel L. Tremblay TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα Immunity & Ageing Inflammaging Macrophages TAOK3 Pro-inflammatory cytokines Chemotaxis |
| title | TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα |
| title_full | TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα |
| title_fullStr | TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα |
| title_full_unstemmed | TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα |
| title_short | TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα |
| title_sort | taok3 limits age associated inflammation by negatively modulating macrophage differentiation and their production of tnfα |
| topic | Inflammaging Macrophages TAOK3 Pro-inflammatory cytokines Chemotaxis |
| url | https://doi.org/10.1186/s12979-023-00350-y |
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