TLR4 Deficiency Impairs Oligodendrocyte Formation in the Injured Spinal Cord.
Jamie S ChurchKristina A KigerlJessica K LerchPhillip G PopovichDana M McTiguePublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2017)
Myelinating cells of the CNS [oligodendrocytes (OLs)] are killed for several weeks after traumatic spinal cord injury (SCI), but they are replaced by resident progenitor cells. How the concurrent inflammatory signaling affects this endogenous reparative response is unclear. Here, we provide evidence that immune receptor toll-like receptor 4 (TLR4) supports OL lineage cell sparing, long-term OL and OL progenitor replacement, and chronic functional recovery. We show that TLR4 signaling is essential for acute iron storage, regulating cytokine and growth factor expression, and efficient myelin debris clearance, all of which influence OL replacement. Importantly, the current study reveals that a single immune receptor is essential for repair responses after SCI, and the potential mechanisms of this beneficial effect likely change over time after injury.
Keyphrases
- toll like receptor
- spinal cord injury
- spinal cord
- growth factor
- inflammatory response
- nuclear factor
- neuropathic pain
- immune response
- single cell
- induced apoptosis
- poor prognosis
- binding protein
- liver failure
- cell cycle arrest
- drug induced
- oxidative stress
- cell therapy
- cell fate
- respiratory failure
- squamous cell carcinoma
- multiple sclerosis
- stem cells
- signaling pathway
- long non coding rna
- gestational age
- replacement therapy
- aortic dissection
- pi k akt
- climate change
- preterm birth
- locally advanced
- iron deficiency
- human health