Interleukin-17A Plays Key Role in Inflammation in MS, Mouse Study Finds

Interleukin-17A Plays Key Role in Inflammation in MS, Mouse Study Finds
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The immune signaling molecule interleukin-17A (IL-17A) promotes the recruiting of inflammatory cells to the central nervous system (brain and spinal cord) in a multiple sclerosis (MS) mouse model, a study found.

The findings support the potential of therapies that target IL-17 in MS. IL-17A is part of the IL-17 family of proteins.

The study “Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1b-Producing Myeloid Cells that Promote Pathogenic T Cells” was published in the journal Immunity.

Immune cells that produce the signaling IL-17 molecule, called Th17 T-cells, have been identified as key mediators of the inflammatory process in several autoimmune diseases, including psoriasis, rheumatoid arthritis, and MS.

In psoriasis, treatment with antibodies that block IL-17 is highly effective. In an early clinical trial with relapsing-remitting MS (RRMS), treatment with an antibody targeting IL-17 — Cosentyx (secukinumab) — yielded promising results.

However, the exact role of IL-17 in MS is still not clear.

Researchers at Trinity College Dublin investigated the role of IL-17 using a mouse model — experimental autoimmune encephalomyelitis (EAE) — that mimics human MS.

Results showed that EAE mice lacking IL-17 were resistant to MS. While all EAE mice developed severe symptoms 20 days after the triggering of inflammation in the brain and spinal cord (encephalomyelitis), only 35% of EAE mice without IL-17 showed clinical signs of the disease, and these were mild in severity.

Researchers found that EAE mice without IL-17 also had significantly fewer immune cells — namely CD4+ and gamma delta T-cells — in the spinal cord. When IL-17 was absent, the levels of IL-1-beta (another immune molecule) were lower.

Researchers looked for cells that could be producing IL-1-beta in response to IL-17. They found that IL-17A mobilized IL-1-beta-secreting immune cells (called neutrophils and inflammatory monocytes) to lymph nodes. In turn, these cells promoted the disease-promoting activity of T-cells in the CNS.

“Our team found that IL-17 plays a critical ‘priming’ role in kick-starting the disease-causing immune response that mediates the damage in EAE and MS,” Kingston Mills, a professor at Trinity’s School of Biochemistry and Immunology, and the study’s lead author, said in a press release.

“The new research shows that, instead of playing a direct part in CNS pathology, a key role of IL-17 is to mobilize and activate an army of disease-causing immune cells in the lymph nodes that then migrate to the CNS to cause the nerve damage,” Mills said.

The findings support the potential of anti-IL-17 therapies in easing MS symptoms. The study also suggests that anti-IL-17 therapies do not need to cross the blood-brain-barrier — a highly selective membrane that shields the CNS from the general blood circulation, and a roadblock in the efficacy of several MS therapies.

“Crucially, our findings suggest that drugs that block IL-17 may not need to get across the blood-brain barrier to be effective in treating MS,” said Aoife McGinley, the study’s first author.

“As well as shedding new light on the importance of IL-17 as a drugs target in RRMS, our research highlights the huge potential of drugs that block IL-17 in the treatment of other autoimmune diseases, such as psoriasis and rheumatoid arthritis” McGinley said.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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