TRISOMY 21 CAUSES GLOBAL CHANGES IN GENE EXPRESSION IN REGULATORY T CELLS

MACCIONI, MARIANA; SULLIVAN, KELLY D; WAUGH, KATHERINE; ESPINOSA, JOAQUIN M; PANDEY, AHWAN; ROSELLI, EMILIANO; SMITH, KEITH; NUÑEZ, NICOLAS GONZALO; ARAYA, PAULA

Buenoa Aires

Congreso; REUNION CONJUNTA DE SOCIEDADES DE BIOCIENCIA. LXV ANNUAL SCIENTIFIC MEETING OF SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2017

CIBICI-SAI

Trisomy 21 (T21) causes Down syndrome, due to the presence of an extra copy of chromosome 21 in some or all of an individual's cells. Individuals with T21 have alterations in disease incidence: these individuals have a higher predisposition of Alzheimer?s disease, leukemia and autoimmune disorders, but a decrease susceptibility to solid tumors compared to euploid individuals (disomic, D21). Also, individuals with T21 present a constant activation of interferon signaling. Recently, we found that regulatory T cells (Treg) from individuals with T21 show an impaired suppressive capacity in vitro with no significant changes in the Treg phenotypic signature. In order to understand why T21 Treg are dysfunctional, we sorted CD4+ CD25hi CD127lo from peripheral blood of T21 and age-matched D21 individuals (n=6) and performed transcriptomic analysis by RNA-seq (using Clontech SMARTer Ultra Low Input RNA kit v4 followed by the Nextera XT kit to create the libraries that were sequenced on the HiSeq 2500). The comparison of T21 versus D21 Treg cells identified 134 consistent differentially expressed genes (DEGs, padj