Talk abstracts
Talk on Tuesday 03:00-03:15pm submitted by Mariam Salem
Emerging Role of Aiolos in Regulating B Cell Central Tolerance
Mariam A Salem (Molecular, Cellular, and Developmental Biology Graduate Program), Kruthika Sharma (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Melissa R Leonard (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Srijana Pokhrel (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Kenneth J Oestreich (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Patrick L Collins (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. )
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 leads to distinct cellular fates. Mutations in specific transcription factors are commonly found in immune cell cancers and immune-based disorders. 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 responsible for the onset of lymphocyte differentiation and its functional outcome. Mutations in Aiolos gene, IKZF3, specifically are linked to several autoimmune diseases characterized by a break in tolerance checkpoints. The molecular mechanisms underlying tolerance regulation remain fairly unknown. Here 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. Moreover, single cell transcriptome analysis, Cut and Run and flow cytometry revealed Aiolos transcriptomic regulation for cell cycle regulators and the chemotaxis receptor CXCR4. We demonstrated that Aiolos has a role for correct selection of non-autoreactive B cells and bypassing the receptor editing stage in B cell central tolerance. 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 and cancers originating from distinct steps in the intricate developmental pathway of B cells.
Keywords: Immunology, Autoimmune diseases, Chromatin