Critical role of Helios in the differentiation of T conventional memory cells

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B728
Abstract ID: 4608

Presenting Author:
Sooho S Myoung , Postbaccalaureate IRTA Fellow at NIAID, NIH

Abstract:

The transcription factor Helios is highly expressed in regulatory T cells (Treg) and in a subset of CD4⁺CD44^hi T conventional (Tconv) memory cells. Mice with Foxp3Cre deletion of Helios develop systemic autoimmunity characterized by hyperproliferation of T cells and autoimmune lipodystrophy. Conversely, mice with CD4Cre deletion of Helios reverses autoimmunity, indicating an important role for Helios in Tconv. To explore the role of Helios in memory T cell subsets, we performed single-cell transcriptome analysis on CD4⁺CD44^hiFoxp3^- splenocytes from wildtype and knockout CD4Cre mice. Cross-sectional comparison revealed substantial differences in cluster composition and gene expression. Notably, SOSTDC1, a secreted  antagonist of the Wnt--catenin signaling pathway, was markedly reduced in memory-like clusters from KO mice. As the Wnt pathway is known to arrest the development of CD8⁺ T cells into effector cells, and since autoimmune lipodystrophy in Helios^fl/fl x Foxp3Cre mice is predominantly mediated by CD8⁺ T cells, we also performed scRNA-seq analysis of CD8⁺ memory cells from wildtype and knockout CD4Cre mice. Memory cell cluster composition was markedly different between the two strains with an increase in the percentage of exhausted cytotoxic effector-like cells in the Helios^fl/fl x CD4Cre mice. These findings suggest that the Helios-mediated regulation of SOSTDC1 in CD4⁺ memory cells may redirect the differentation of memory T cells.