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. 2021 Jun 25;12:621440. doi: 10.3389/fimmu.2021.621440

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Copyright © 2021 Illouz, Biragyn, Iulita, Flores-Aguilar, Dierssen, De Toma, Antonarakis, Yu, Herault, Potier, Botté, Roper, Sredni, London, Mobley, Strydom and Okun

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Immune dysregulation in DS. Left panel; Innate immunity impairments in DS include a decrease in CD14⁺⁺CD16^- monocytes, an increase in CD14⁺CD16⁺ monocytes, increase in NK cells, a decrease in myeloid dendritic cells (mDC), and a decrease in granulocytes. Neutrophils exhibit dysregulated Ca⁺⁺ homeostasis and reduced chemotactic ability, which results in impaired functionality. Middle panel; humoral response dysregulation includes a decrease in total IgG, as well as IgG and IgA levels in the saliva. Specifically, of IgG2, IgG4, and IgM production levels decrease, while production levels of IgG1, IgG3 and IgA increase. Right panel; Adaptive immunity impairments include a decrease in the numbers of CD4⁺ T cells, an increase in the numbers of CD8⁺ cells, and a decrease in the number of T regulatory cells. Overall, fewer T cells in DS express the αβ subunits of the T-cell receptor (TCR), and more T cells express the γδ subunits of the TCR. The numbers of B cells and switched memory B cells also decrease in DS.