Pluto Bioinformatics

GSE92395: Neural precursor cell-secreted TGF-2 subverts the inflammatory program of invading monocyte-derived dendritic cells during CNS autoimmunity

Bulk RNA sequencing

In Multiple Sclerosis, the pathological interaction of autoreactive helper T (TH) cells with mononuclear phagocytes in the central nervous system (CNS) drives initiation and maintenance of chronic neuroinflammation. Herein, we found that intrathecal transplantation of neural stem cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived dendritic cells (moDCs) in the CNS leading to improved clinical outcome. NPCs treatment reduced in the CNS IL-23, IL-1 and TNF-, cytokines required for terminal differentiation of TH cells and accordingly GM-CSF-producing pathogenic TH cells. In vivo and in vitro transcriptome analyses disclosed that NPC secreted factors induce an inhibition of DC differentiation and maturation, favoring a fate switch towards an anti-inflammatory phenotype. We identified TGF-2 as the crucial mediator of NPC immunomodulation: TGF2 knockout NPCs transplanted in EAE are ineffective in impairing moDC accumulation within the CNS and fail to drive clinical improvement. This study provides evidence that intrathecally injected NPCs interfere with CNS-compartmentalized inflammation of the effector phase of EAE, reprogramming, through the secretion of TGF-2, inflammatory monocyte-derived DCs towards anti-inflammatory myeloid cells. SOURCE: Jose,Manuel,Garcia-Manteiga (garciamanteiga.josemanuel@hsr.it) - OSR - San Raffaele Scientific Institute