scholarly journals TNFR2 Signaling Regulates the Immunomodulatory Function of Oligodendrocyte Precursor Cells

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1785
Author(s):  
Haritha L. Desu ◽  
Placido Illiano ◽  
James S. Choi ◽  
Maureen C. Ascona ◽  
Han Gao ◽  
...  

Multiple sclerosis (MS) is a neuroimmune disorder characterized by inflammation, CNS demyelination, and progressive neurodegeneration. Chronic MS patients exhibit impaired remyelination capacity, partly due to the changes that oligodendrocyte precursor cells (OPCs) undergo in response to the MS lesion environment. The cytokine tumor necrosis factor (TNF) is present in the MS-affected CNS and has been implicated in disease pathophysiology. Of the two active forms of TNF, transmembrane (tmTNF) and soluble (solTNF), tmTNF signals via TNFR2 mediating protective and reparative effects, including remyelination, whereas solTNF signals predominantly via TNFR1 promoting neurotoxicity. To better understand the mechanisms underlying repair failure in MS, we investigated the cellular responses of OPCs to inflammatory exposure and the specific role of TNFR2 signaling in their modulation. Following treatment of cultured OPCs with IFNγ, IL1β, and TNF, we observed, by RNA sequencing, marked inflammatory and immune activation of OPCs, accompanied by metabolic changes and dysregulation of their proliferation and differentiation programming. We also established the high likelihood of cell–cell interaction between OPCs and microglia in neuroinflammatory conditions, with OPCs able to produce chemokines that can recruit and activate microglia. Importantly, we showed that these functions are exacerbated when TNFR2 is ablated. Together, our data indicate that neuroinflammation leads OPCs to shift towards an immunomodulatory phenotype while diminishing their capacity to proliferate and differentiate, thus impairing their repair function. Furthermore, we demonstrated that TNFR2 plays a key role in this process, suggesting that boosting TNFR2 activation or its downstream signals could be an effective strategy to restore OPC reparative capacity in demyelinating disease.

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Fang Li ◽  
Mou-Wang Zhou ◽  
Nan Liu ◽  
Yan-Yan Yang ◽  
Hua-Yi Xing ◽  
...  

MicroRNA-219 (miR-219) regulates the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) during central nervous system (CNS) development. OPCs only differentiate into oligodendrocytes (OLs) in the healthy CNS, but can generate astrocytes (As) after injury. We hypothesized that miR-219 may modulate OPC proliferation and differentiation in a cervical C5 contusion spinal cord injury (SCI) model. After injury, we observed a decrease in the miR-219 level and quantity of OLs and an increase in the number of OPCs and As. Silencing of miR-219 by its antagomir in vivo produced similar results, but of greater magnitude. Overexpression of miR-219 by its agomir in vivo increased the number of OLs and suppressed generation of OPCs and As. Luxol fast blue staining confirmed that SCI caused demyelination and that the extent of demyelination was attenuated by miR-219 overexpression, but aggravated by miR-219 reduction. Monocarboxylate transporter 1 (MCT-1) may be implicated in the regulation of OPC proliferation and differentiation mediated by miR-219 following contusion SCI. Collectively, our data suggest that miR-219 may mediate SCI-induced OPC proliferation and differentiation, and MCT-1 may participate in this process as a target of miR-219.


2017 ◽  
Vol 8 (6) ◽  
pp. e2871-e2871 ◽  
Author(s):  
Elisabetta Bonfanti ◽  
Paolo Gelosa ◽  
Marta Fumagalli ◽  
Leda Dimou ◽  
Francesca Viganò ◽  
...  

Author(s):  
Natsue Kishida ◽  
Takakuni Maki ◽  
Yasushi Takagi ◽  
Ken Yasuda ◽  
Hisanori Kinoshita ◽  
...  

Glia ◽  
2013 ◽  
Vol 61 (5) ◽  
pp. 732-749 ◽  
Author(s):  
Cui Li ◽  
Lin Xiao ◽  
Xiuyun Liu ◽  
Wenjing Yang ◽  
Weiran Shen ◽  
...  

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Noel G. Carlson ◽  
Satya Bellamkonda ◽  
Linda Schmidt ◽  
Jonathan Redd ◽  
Thomas Huecksteadt ◽  
...  

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