Multiple Sclerosis: How TH17 Cells Drive Disease and Shape Treatment
Multiple sclerosis (MS) has long puzzled scientists and clinicians alike. A complex immune-mediated disease that attacks the central nervous system (CNS), MS leads to inflammation, demyelination, and ultimately neurological disability. But what if the key to understanding MS — and effectively treating it — lies in a specific subset of immune cells?
A 2020 review by Moser et al., published in Autoimmunity Reviews, dives deep into this exact question, focusing on a powerful group of immune players known as TH17 cells. Here’s a human-friendly breakdown of what they found and why it matters.
What Are TH17 Cells?
TH17 cells are a type of CD4+ T helper cell that produce the inflammatory cytokine interleukin-17 (IL-17). These cells only make up about 3% of the total T helper population, but don’t be fooled by their small numbers — they pack a punch when it comes to causing inflammation, especially in autoimmune diseases like MS.
Over time, scientists have discovered that TH17 cells aren’t a uniform group. They can evolve, adapt to their environment, and even transform into hybrid cells with traits from other T cell types. This dynamic behavior makes them particularly relevant — and dangerous — in MS.
Meet the Culprit: TH17.1 Cells
Within the broader TH17 family, a subpopulation called TH17.1 cells stands out. These are cells that start as classical TH17 cells but go on to express interferon-gamma (IFN-γ), a signature cytokine of TH1 cells. The result? A hybrid cell that is even more inflammatory and destructive — like giving an already dangerous flame-thrower a turbo boost.
TH17.1 cells are experts at breaking through the blood-brain barrier (BBB) and infiltrating the CNS. They also resist suppression by regulatory T cells (Tregs) and may even evade some immunosuppressive therapies, making them prime suspects in MS disease progression and relapse.
Evidence Piling Up: Why TH17 Cells Matter in MS
The paper presents a six-pronged case for the central role of TH17 cells in MS:
Animal Studies: Mice lacking key TH17-related cytokines (like IL-23 or IL-17) are resistant to developing MS-like disease.
Histopathology: Active MS lesions are teeming with IL-17-producing T cells.
Genetics: Several MS-associated genes, including those for IL-17 and its receptor, point toward TH17 involvement.
Environmental Factors: Vitamin D, high salt intake, and gut bacteria all influence TH17 cell development — and MS risk.
Laboratory Evidence: People with MS have elevated TH17 cells in blood and spinal fluid, especially during relapses.
Drug Responses: Effective MS treatments consistently target TH17 cells or their pathways.
TH17 Cells and MS Treatments: A Therapeutic Hit List
One of the most compelling insights from Moser et al.’s review is how many MS drugs — even those with different mechanisms — impact TH17 cells. Here's a snapshot:
Fingolimod & Alemtuzumab: Reduce central memory TH17 and TH17.1 cells.
Natalizumab: Blocks CNS entry of TH17.1 cells by targeting their "entry pass" — the VLA-4 receptor.
Anti-CD20 Therapies (e.g., Ocrelizumab): Though originally targeting B cells, these drugs also deplete TH17-like CD20+ T cells and reduce IL-6, which fuels TH17 development.
Dimethyl Fumarate: Inhibits pro-inflammatory T cells and supports anti-inflammatory ones.
Interferon-beta & Glatiramer Acetate: Dampen IL-17 production and shift the balance away from inflammation.
Cladribine & Stem Cell Therapy: Profoundly deplete TH17 subsets, especially the more aggressive ones.
What This Means for MS Patients
The take-home message? TH17 and especially TH17.1 cells are not just bystanders — they are central actors in the MS story. Nearly all effective therapies tamp down their numbers or block their function. Tracking TH17 levels may help predict relapses, guide treatment choices, and even inform new drug development.
Looking Ahead
MS is a complex disease with many layers, but research like this peels back some of that complexity. By focusing on TH17 and TH17.1 cells, scientists are not only getting closer to understanding how MS develops but also how to stop it more effectively.
As future therapies evolve, we may move toward more personalized MS care — targeting specific immune profiles in each patient. Until then, TH17 cells will remain firmly in the spotlight of MS research.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Moser, T., Akgün, K., Proschmann, U., Sellner, J., & Ziemssen, T. (2020). The role of TH17 cells in multiple sclerosis: Therapeutic implications. Autoimmunity reviews, 19(10), 102647.
