Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity.

: P. ARAYA, N. NUÑEZ, D.A.NOCERA, E. ROSELLI, M. MACCIONI

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2020 vol. 116 p. 24231 - 24231

0027-8424

risomy 21 (T21) causes Down syndrome (DS), a condition characterized by high prevalence of autoimmune disorders. However, the molecular and cellular mechanisms driving this phenotype remain unclear. Building upon our previous finding that T cells from people with DS show increased expression of interferon (IFN)-stimulated genes, we have completed a comprehensive characterization of the peripheral T cell compartment in adults with DS with and without autoimmune conditions. CD8+ T cells from adults with DS are depleted of naïve subsets and enriched for differentiated subsets, express higher levels of markers of activation and senescence (e.g., IFN-γ, Granzyme B, PD-1, KLRG1), and overproduce cytokines tied to autoimmunity (e.g., TNF-α). Conventional CD4+ T cells display increased differentiation, polarization toward the Th1 and Th1/17 states, and overproduction of the autoimmunity-related cytokines IL-17A and IL-22. Plasma cytokine analysis confirms elevation of multiple autoi