Ulk1 regulates T Cell Development and Response to Listeria monocytogenes Stimulation.

ABSTRACT

T cells are crucial for the normal functioning of the immune system. The development and response of these cells to foreign antigens involve many complex stages and interactions between various types of cells. However, many details of these processes are still unclear. Our research revealed a key role for a protein called ULK1, a serine/threonine protein kinase, in regulating T-cell development and function. During T-cell maturation, the absence of Ulk1 (as in Ulk1-/- mice) leads to an increase in a cell type called DN3 in the thymus. We also found a reduction in the number of T cells in peripheral immune organs, such as the spleen, in Ulk1-/- mice. In response to Listeria infection, Ulk1-/- mice have a weaker ability to clear this bacterium, and their T cells also have defects in producing cytokines. However, the absence of Ulk1 did not affect the activation or apoptosis of naïve CD4+ T cells in vitro. In a bone marrow chimeric mouse model, T cells from Ulk1-/- mice did not differ developmentally from those from control mice. Furthermore, RNA-seq revealed that Ulk1 deficiency affects the metabolic function of splenocytes and T-cell function in mice, potentially through the canonical Wnt signaling cascade and the ERK1/ERK2 signaling cascades. Overall, these results suggest that Ulk1 is essential for T-cell maturation in the thymus, the balance of peripheral T cells, and the functional response of T cells to antigens.