Mohammad Nematullah, et al. – Henry Ford Hospital.
Background: The mechanisms triggering excessive immune activity in MS remain largely unknown. One key regulator of immune function in numerous contexts is itaconate, an offshoot of the citric acid cycle produced by Immune-Responsive Gene 1 (Irf1).
This Study:
- Nematullah and colleagues examined the impact of knocking-out (KO) Irf1 on immune cells, both in vitro and in the context of the experimental autoimmune encephalitis (EAE) model of MS.
- Irf1 KO mice showed more severe clinical symptoms in the EAE protocol, as did WT mice provided with Irf1 KO CD4+ T cells that were primed against MOG35-55 compared to those given primed WT CD4+ cells.
- Loss of Irf1 was associated with greater antigen presentation, production of inflammatory cytokines such as IL-1β, and NLRP3 inflammasome generation in macrophages, as well as a bias of Th17 helper T cells towards a pathogenic phenotype.
Bottom Line: Irf1 is a key negative regulator of autoimmune activity; increasing its activity and/or providing patients with itaconate may curb symptoms and inflammation.
