The emerging role of Aiolos in regulating B and T cell tolerance

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B613
Abstract ID: 5723

Presenting Author:
Mariam A Salem , Graduate Student at Ohio State Univ. Col. of Med.

Abstract:

Lymphocyte functionality and the determination of their fate are intricately linked to transcriptional and epigenetic regulation. These processes are influenced by stage and lineage-specific transcription factors which in combination lead to distinct cellular fates. Mutations in specific transcription factors are commonly found in immune-based disorders. Studying these mutations not only offer a deeper understanding of lymphocyte homeostasis but also pave the way for treatment approaches in human illnesses. One such significant transcription factor is Aiolos, member of the Ikaros family. Mutations in the Aiolos gene, IKZF3, are linked to several autoimmune diseases characterized by a break in tolerance. The molecular mechanisms underlying tolerance regulation remain fairly unknown. We report a novel role for Aiolos in regulating B and T cell tolerance. Examination of the bone marrow, spleen and thymus of Ikzf3^-/- mice revealed defects in B and T cell development and migration. Single cell transcriptome analysis, Cut & Run and flow cytometry revealed Aiolos transcriptomic regulation for cell cycle regulators and the chemotaxis receptor CXCR4 among other targets. We show that Aiolos plays a role in bypassing the receptor editing stage during B cell central tolerance, facilitating the selection of non-autoreactive B cells. Insight into the mechanisms by which Aiolos regulates and is in turn regulated can provide new approaches to alter the outcome of immune cell disorders.