Academic Journal
Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology
| العنوان: | Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology |
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| المؤلفون: | Takeda, Andrew J., Maher, Timothy J., Zhang, Yu, Lanahan, Stephen M., Bucklin, Molly L., Compton, Susan R., Tyler, Paul M., Comrie, William A., Matsuda, Makoto, Olivier, Kenneth N., Pittaluga, Stefania, McElwee, Joshua J., Long Priel, Debra A., Kuhns, Douglas B., Williams, Roger L., Mustillo, Peter J., Wymann, Matthias P., Koneti Rao, V., Lucas, Carrie L. |
| المساهمون: | Division of Intramural Research, National Institute of Allergy and Infectious Diseases, U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases, U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute, U.S. Department of Health & Human Services | NIH | National Cancer Institute, British Heart Foundation, Department of Health | National Health and Medical Research Council |
| المصدر: | Nature Communications ; volume 10, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2019 |
| الوصف: | Phosphatidylinositol 3-kinase-gamma (PI3Kγ) is highly expressed in leukocytes and is an attractive drug target for immune modulation. Different experimental systems have led to conflicting conclusions regarding inflammatory and anti-inflammatory functions of PI3Kγ. Here, we report a human patient with bi-allelic, loss-of-function mutations in PIK3CG resulting in absence of the p110γ catalytic subunit of PI3Kγ. She has a history of childhood-onset antibody defects, cytopenias, and T lymphocytic pneumonitis and colitis, with reduced peripheral blood memory B, memory CD8+ T, and regulatory T cells and increased CXCR3+ tissue-homing CD4 T cells. PI3Kγ-deficient macrophages and monocytes produce elevated inflammatory IL-12 and IL-23 in a GSK3α/β-dependent manner upon TLR stimulation. Pik3cg -deficient mice recapitulate major features of human disease after exposure to natural microbiota through co-housing with pet-store mice. Together, our results emphasize the physiological importance of PI3Kγ in restraining inflammation and promoting appropriate adaptive immune responses in both humans and mice. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-019-12311-5 |
| الاتاحة: | http://dx.doi.org/10.1038/s41467-019-12311-5 https://www.nature.com/articles/s41467-019-12311-5.pdf https://www.nature.com/articles/s41467-019-12311-5 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.959E7AFE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-12311-5 |
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