| Autor: |
Hyeseok Shim, Chuan Wu, Ramsamooj, Shivan, Bosch, Kaitlyn N., Zuojia Chen, Emerling, Brooke M., Jihye Yun, Hui Liu, Rayman Choo-Wing, Zhiwei Yang, Wulf, Gerburg M., Kuchroo, Vijay Kumar, Cantley, Lewis C. |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 7/5/2016, Vol. 113 Issue 27, p7596-7601, 6p |
| Abstrakt: |
Type 2 phosphatidylinositol-5-phosphate 4-kinase (PI5P4K) converts phosphatidylinositol-5-phosphate to phosphatidylinositol-4,5-bisphosphate. Mammals have three enzymes PI5P4Kα, PI5P4Kβ, and PI5P4Kγ, and these enzymes have been implicated in metabolic control, growth control, and a variety of stress responses. Here, we show that mice with germline deletion of type 2 phosphatidylinositol-5- phosphate 4-kinase gamma (Pip4k2c), the gene encoding PI5P4Kγ, appear normal in regard to growth and viability but have increased inflammation and T-cell activation as they age. Immune cell infiltrates increased in Pip4k2c-/- mouse tissues. Also, there was an increase in proinflammatory cytokines, including IFNγ, interleukin 12, and interleukin 2 in plasma of Pip4k2c-/- mice. Pip4k2c-/- mice had an increase in T-helper-cell populations and a decrease in regulatory T-cell populations with increased proliferation of T cells. Interestingly, mammalian target of rapamycin complex 1 (mTORC1) signaling was hyperactivated in several tissues from Pip4k2c-/- mice and treating Pip4k2c-/- mice with rapamycin reduced the inflammatory phenotype, resulting in a decrease in mTORC1 signaling in tissues and a decrease in proinflammatory cytokines in plasma. These results indicate that PI5P4Kγ plays a role in the regulation of the immune system via mTORC1 signaling. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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