Effect of abrogated DNA-binding of thyroid hormone receptor alpha on the gene expression in CD25- CD4+ naive T cells and CD25+ CD4+ regulatory T cells

Thyroid hormones (TH) have emerged as important regulators of the immune system, mediating pro- and anti-inflammatory actions. However, the role of TH in T cells, which are central players of protective immunity has remained largely elusive. To address the impact TH on CD4 T cell immunity, we used RNA-sequencing analysis of naive CD4 T cells and Treg isolated from spleens of mice with a mutation in the DNA binding domain of TRa (TRaGS) or WT littermates. In absence of canonical TRa signaling gene expression profile of naive CD4 T cells was altered with enriched differential expression of genes involved in T cell homeostasis and migration. In TRaGS Treg increased expression of activation and migratory markers was found. Moreover, abrogated canonical TRa signaling was also related to changes in NF?B signaling pathway in Treg, which has been previously related to Treg induction and function. Hence, our findings provide new insight in the effect of canonical TRa singlaing in CD4 T cell immunity. Overall design: To investigate the impact of TRa signaling on differentiation and function of Treg we isolated CD25- CD4+ naive T cells as well as CD25+ CD4+ Treg from spleen of TRaGS mice and WT littermates by FACS. Gene expression profile of isolated cells was determined and gene expression profiles of genotypes wihtin both T cell subsets were compared.