Thymocyte development and transcription factor expression are disrupted by Runx2 deficiency 2259108

Abstract Introduction Transcriptional regulation during T cell development in the thymus is critical for the maturation of naive T cells that will seed the periphery. Several key signals, including T cell receptor signaling and co-stimulation, impact expression of transcription factors which guide thymocyte fate via processes such as survival and lineage commitment. Runt-related transcription factors (Runx) have been described as key mediators of development processes for several lymphocyte subsets. While Runx1 and Runx3 have been demonstrated to impact CD8 T cell development, studies on Runx2 are limited. Findings from experiments using Runx2 overexpressing mice suggest a role of Runx2 in β-selection during the double-negative stage of T cell development. Whether deficiency in Runx2 impacts thymocyte development at stages other than β-selection is currently unknown. Methods To explore whether Runx2 has a key role in T cell maturation, we evaluated its expression in thymocytes by flow cytometry and analyzed double-negative (DN), double-positive (DP), and single-positive (SP) T cell development in 5-week-old C57BL/6J wild-type and T cell-conditional Runx2-deficient (runx2-/-) mice. Results We found that while Runx2 expression varied by T cell maturation stage, Runx2 was highly expressed in DN thymocytes. Accordingly, the frequency of DN thymocyte subsets was altered in the thymus of runx2-/- mice when compared to the frequency present in wild-type mice. SP CD4 and CD8 T cell maturation, as measured by CD24 expression, was also impaired in T cell conditional runx2-/- deficient mice. Furthermore, expression of the transcription factors Runx3, ID2, and RORγT was altered in select runx2-/- thymocyte subsets. Conclusion Together, our results suggest that the transcription factor Runx2 is involved in the transcriptional coordination of thymocyte development and maturation. These and future studies aim to help further understand the role of Runx2 in the formation of mature T cells. Funding Source UCF Foundation Topic Categories Hematopoiesis and Immune System Development (HEM)