Phenotypical and Functional Characterization of Meningeal Localized Regulatory T cells

Abstract

The regulatory T cells (Treg) population is characterized by their unique immunoregulatory functions. Recently, more and more evidence has elucidated Tregs’ roles beyond immune suppression, such as its ability to facilitate tissue and organismal homeostasis. The tissue localized Tregs have been identified at various tissue sites, such as fat, skin, lung, and colon, along with tissue-specific phenotypical and functional adaptations. However, many other tissue sites are yet to be explored. The central nervous system (CNS) was traditionally viewed as the "immune privileges" site, while recent studies show that CNS is under constant immune surveillance. Many studies have shown that meningeal immunity and Tregs are critical to CNS function and pathogenesis. However, these studies focused on the circulating Tregs rather than the tissue localized Treg population. Previous work in the lab has identified meningeal localized Tregs in healthy mice. We hypothesized that meningeal Tregs help maintain brain CNS homeostasis by interacting with cells in the brain CNS, including meningeal stromal cells, neurons, glial cells, and other types of immunocytes via direct contact or secretion of cytokines and other mediators. By utilizing pre-defined CNS processes and disease signatures as well as applying population-level RNA sequencing and gene set enrichment analysis on differentially expressed genes identified post acute Treg depletion, we found that the ablation of Tregs induced local activation of type I and II interferons signaling pathway in the CNS. Our findings suggest that meningeal Tregs regulate type I and II interferon production, which then impacts various processes and cells across CNS regions under the steady and diseased state. Our observation could suggest new perspectives on studying CNS-immune interactions and identifying new therapeutic approaches to treat CNS diseases.