Newly Discovered Immune Cells can Help Fight CNS Damage

By Sahana Shankar, Ph.D. Candidate

Neurons are terminally differentiated cells and cannot be regenerated for the most part. Hence, neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) have no cure since these are caused by gradual and progressive degeneration of the nervous system. In a new breakthrough, researchers at the Ohio State University Wexner Medical Center and the University of Michigan have discovered a new subclass of immune cells that can protect neurons from death and reverse damage in nerve fibers due to injury.

Reengineering the immune system to limit the damage to the central nervous system (CNS) is a potential therapeutic approach that needs a thorough understanding of the various immune cell populations and their function. Zymosan, a fungal cell wall component, has been established as a neuroprotective agent that induces neuroinflammation in injured retinal ganglion cells to prevent their degeneration in vitro. To understand how zymosan confers neuroprotection, this study used a mouse model of an injured eye or lacerated nerve fibers, injected with zymosan, and studied the immune system’s response.

Newly Discovered Neutrophils

The authors discovered a class of immature neutrophils in the vitreous fluid, which could drive axon regrowth and showed neuro regenerative properties. While probing the cause of neuroprotection, the team found that these neutrophils secrete growth factors such as nerve growth factor or insulin-like growth factor-1. These factors may promote the proliferation of retinal ganglion cells (RGCs) and enhance nerve fibers’ growth and improve the survival of neurons post-injury by stimulating cell proliferation, which is a remarkable deviation from current knowledge. “In the future, this line of research might ultimately lead to the development of novel cell-based therapies that restore lost neurological functions across a range of conditions,” said lead author Dr. Benjamin Segal, MD Ph.D., Professor of Neurology at the Ohio State College of Medicine.

Injecting the immature neutrophils into the injured mice resulted in new neurons and promoted repair and regeneration in the optic nerve and spinal cord, suggesting that these immune cells can stimulate regeneration across the span of the central nervous system. The results were reproducible in a human cell line with properties of the immature neutrophils, making it highly likely that these cells could be relevant in the clinic to be used along with compounds that promote neuron growth to enhance regeneration. This holds tremendous promise to find possible cell-based therapies to reverse CNS damage and promote neuroprotection.

Potential Implications

Next, the team plans to isolate, characterize, and improve these immune cells for their regenerative and therapeutic capacity to develop cell therapy for patients across the spectrum of neurodegenerative diseases. “I treat patients who have permanent neurological deficits, and they have to deal with debilitating symptoms every day. The possibility of reversing those deficits and improving the quality of life of individuals with neurological disorders is very exciting. There’s so much that we’re learning at the bench that has yet to be translated to the clinic, I think there’s huge potential for future medical breakthroughs in our field,” Segal said.

Related Article: Availability of C2N’s First Blood-Based Diagnostic Marks Breakthrough in Alzheimer’s Disease

References

1. https://www.nature.com/articles/s41590-020-00813-0
2. https://wexnermedical.osu.edu/mediaroom/pressreleaselisting/discovery-of-new-cell-may-be-key-to-treating-incurable-neurological-diseases

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Author

Sahana Shankar