Microvilli shedding and its physiological implications in T cell immunity

Abstract

In the contact between T cells and APCs, T cell microvilli help physically bind to APCs and control immune T cells to be stimulated appropriately as containing various immune-activating factors. Finally, most T cell microvilli are released upon the reaction's termination with APCs. This transfer of microvilli and surface proteins to other cells may seem unfavorable to the T cell itself. Although recent studies have emphasized the importance of T cell microvilli, the influence of microvilli shedding is still poorly understood from the viewpoint of T cells.

In PART 1 of this study, we define "Trogocytic-molting" as the loss of membrane that T cells experience during activation, explaining the physiological significance of this phenomenon. Trogocytic-molting significantly reduced the number of microvilli but stimulated clonal expansion in T cells. In addition, we reveal that the tendency of metabolism and differentiation of naive T cells could vary depending on the degree of release of T cell microvilli.

In PART 2, it was revealed that the over-exposure of CS, a naturally biosynthesized cholesterol derivative, depletes the microvilli of T cells. T cells with microvilli defects caused by excessive CS did not properly form immune synapses, and the activation of the TCR-downstream signal decreased. We used CS as an immunosuppressive agent and applied it to treating atopic disease. As a result, it was confirmed that atopic inflammation and lesions were alleviated in Balb/c mice. Based on two studies, this paper proposes understanding the physiological meaning of microvilli shedding in immune T cells and expects therapeutic effects for specific diseases by using microvillus-related characteristics.