Project R-14253

IL-34 mediates a novel non-canonical function of regulatory T cells by protecting brain barriers in neuroinflammation (Research)

Disruption of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) is an early and crucial event in the development of autoimmune disease multiple sclerosis (MS). This event opens a gateway for immune cells into the brains, resulting in damage to nerve cells. Targeting these barriers has great potential to prevent disease progression. Our preliminary data show that the lack of a special type of immune cell, the regulatory T cells (Tregs), mainly known for their controlling function, leads to decreased brain barrier integrity in mice. I hypothesize that this novel, non-canonical function is mediated by production of the molecule IL-34. Indeed, our data show that Tregs produce IL-34, which is hampered in relapsing-remitting MS. Even more, IL-34 protects against brain barrier disruption in several of our cell models. Using mouse and cell models of both brain barriers during brain inflammation, this project will reveal a novel non-canonical, regenerative function of Tregs, being the protection of brain barriers by IL-34 production. In addition, I will explore MS-specific disturbances in the IL-34 response in Tregs. Altogether, harnessing this knowledge will contribute to the development of a long-lasting, reparative Treg-based therapies for MS and by extension for other neurological disorders.

01 November 2023 - 31 October 2027