# Regnase-1 in cDC1 controls T cell priming and shapes the dynamics of experimental autoimmune encephalomyelitis

## TL;DR

This study shows how a protein called Regnase-1 in a type of immune cell affects both inflammation and recovery in a mouse model of a brain disease.

## Contribution

The study reveals a dual role for Regnase-1 in cDC1 cells, balancing acute inflammation and immune memory during disease.

## Key findings

- Reduced Regnase-1 in cDC1 increases pro-inflammatory gene expression and T cell activation.
- Mice with reduced Regnase-1 in cDC1 show faster disease progression and more Th1 and CD8+ T cell infiltration in the CNS.
- These mice also recover faster with increased central memory CD8+ T cells.

## Abstract

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS), in which various immune cells contribute to disease progression, yet the role of dendritic cells (DCs) remains incompletely understood. The RNA-binding protein Regnase-1 plays an important role in regulating immune cell function, but its function in DCs, particularly conventional type 1 DCs (cDC1), has not been defined.

We investigated the role of Regnase-1 in cDC1 and its impact on experimental autoimmune encephalomyelitis (EAE) on Regnase-1fl/+ Xcr1-Cre+ and control mice.

Reduced Regnase-1 expression in cDC1 enhanced pro-inflammatory gene expression and increased their capacity to activate T cells. In the EAE model, Regnase-1fl/+ Xcr1-Cre+ mice displayed accelerated inflammatory progression during the acute phase, accompanied by increased infiltration of Th1 cells and activated CD8+ T cells in the CNS. Subsequently, Regnase-1fl/+ Xcr1-Cre+ mice showed accelerated recovery, together with increased frequencies of central memory CD8+ T (Tcm) cells.

Our study reveals the complex role for cDC1 with reduced Regnase-1 expression in inflammatory regulation, exacerbating inflammatory responses during the acute phase, while facilitate recovery. This dual role highlights Regnase-1 in cDC1 as a critical regulator that balances inflammation and immune memory.