Dock2 deficiency reveals abnormal activation and differentiation of T cells under the physiological condition

Previous research has demonstrated that Dock2 deficiency results in a reduction in both the quantity and proliferation rate of T cells, thereby heightening the host's vulnerability to various infections. Nevertheless, the impact of DOCK2 on T cell activation remains unexplored. In this study, we employed flow cytometry to assess the activation phenotype of T cells in the peripheral lymphoid tissues of wild-type (Dock2^+/+), DOCK2 heterozygous (Dock2^+/-) and DOCK2 knockout (Dock2^-/-) mice. Our findings revealed that, in comparison to Dock2^+/+ mice, Dock2^-/- mice exhibited increased expression levels of CD44 and CD69 on CD4⁺ and/or CD8⁺ T cells within spleen and mesenteric lymph nodes (MLN). Additionally, there was a significant elevation in the proportions of IFN-γ⁺/CD4⁺, IFN-γ⁺/CD8⁺ and IL-4⁺/CD8⁺ T cells. Furthermore, the percentage of IL-17a⁺/CD4⁺ and IL-17a⁺/CD8⁺ T cells in the MLN of Dock2^-/- mice was higher than that observed in Dock2^+/+ mice. These results suggest that Dock2 deficiency induces aberrant T cell activation in peripheral lymphoid tissues. To further investigate the underlying mechanisms of this phenomenon, we conducted transcriptome sequencing on CD8⁺ T cells collected from all groups of mice. The results indicate that Ccr2 and Ifng are potentially pivotal genes involved in the aberrant activation of T cells in Dock2^-/- mice. These findings contribute to elucidating the host defense mechanisms against foreign pathogens and advance our comprehension of the role of cytoskeleton-related proteins in the regulation of cellular immunity.