Stressed-Out T Cells Fragment the Mind

Abstract

The immune system is increasingly recognized to play an integral role in regulating stress responses. In a recent article in Cell, Fan et al. demonstrate a novel mechanism through which stress drives mitochondrial fragmentation-induced xanthine accumulation in mouse CD4⁺ T cells, subsequently acting on oligodendrocytes to induce anxiety-like behaviors.

Figure 1.. Stress-induced mitochondrial dysfunction in CD4⁺ T cells induces anxiety through oligodendrocyte adenosine receptors in mice.

Stress induces mitochondrial fragmentation and respiratory dysfunction in CD4⁺ T cells, leading to increased xanthine accumulation. This CD4⁺ T cell-produced xanthine functions on oligodendrocyte adenosine A1 receptors to promote anxiety-like behavior in stressed mice (depicted as a cross (elevated plus maze) and a grid (open field test), in mouse behavioral tests). This figure was created using  BioRender (https://biorender.com/).