| Autor: |
Katherine A. Waugh, Paula Araya, Ahwan Pandey, Kimberly R. Jordan, Keith P. Smith, Ross E. Granrath, Santosh Khanal, Eric T. Butcher, Belinda Enriquez Estrada, Angela L. Rachubinski, Jennifer A. McWilliams, Ross Minter, Tiana Dimasi, Kelley L. Colvin, Dmitry Baturin, Andrew T. Pham, Matthew D. Galbraith, Kyle W. Bartsch, Michael E. Yeager, Christopher C. Porter, Kelly D. Sullivan, Elena W. Hsieh, Joaquin M. Espinosa |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 29, Iss 7, Pp 1893-1908.e4 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.10.038 |
| Popis: |
Summary: People with Down syndrome (DS; trisomy 21) display a different disease spectrum relative to the general population, including lower rates of solid malignancies and higher incidence of neurological and autoimmune conditions. However, the mechanisms driving this unique clinical profile await elucidation. We completed a deep mapping of the immune system in adults with DS using mass cytometry to evaluate 100 immune cell types, which revealed global immune dysregulation consistent with chronic inflammation, including key changes in the myeloid and lymphoid cell compartments. Furthermore, measurement of interferon-inducible phosphorylation events revealed widespread hypersensitivity to interferon-α in DS, with cell-type-specific variations in downstream intracellular signaling. Mechanistically, this could be explained by overexpression of the interferon receptors encoded on chromosome 21, as demonstrated by increased IFNAR1 surface expression in all immune lineages tested. These results point to interferon-driven immune dysregulation as a likely contributor to the developmental and clinical hallmarks of DS. : Waugh et al. undertook deep mapping of the immune system in adults with trisomy 21, revealing global immune dysregulation reminiscent of inflammatory states, concurrent with widespread hypersensitivity to IFN-α. These data highlight immune dysregulation and IFN hyperactivity as contributors to the comorbidities more common in people with Down syndrome. Keywords: Down syndrome, trisomy 21, mass cytometry, CyTOF, immune dysregulation, single cell, interferon, JAK/STAT, autoimmunity, inflammation |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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