Key immune trigger identified that may be a central player in MS progression

Posted on: 19 February 2026

Trinity College Dublin researchers have published a new study on MS that has uncovered evidence that a key immune system switch, known as the NLRP3 inflammasome, may play a significant role in the inflammatory processes associated with the pathogenesis of MS. This research emphasizes that this key immune system switch should be targeted with new medicines in MS.

Multiple Sclerosis (MS) is a disorder that targets the brain and spinal cord, leading to impaired nervous system function and a variety of symptoms that include pain, fatigue, muscle spasticity and loss of mobility. It is the most common cause of progressive neurological disability in young adults, preferentially affecting women between 20 and 40 years of age. Some 2.8 million people have MS worldwide, and over 9,000 people in Ireland currently have an MS diagnosis.  

Onset and progression of MS is variable among individuals, and hence the disorder is broadly classified into three subtypes based solely on clinical phenotyping: (i) relapsing remitting MS (RRMS), (ii) secondary progressive MS (SPMS), and (iii) primary progressive MS (PPMS).

Currently there is no cure for MS, and a range of therapies are available to suppress inflammation in MS, however, there is a pressing need for new medicines as approved medications for MS often have a limited ability to block disability progression, and are commonly linked to side effects.

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Key Findings

The researchers took an innovative approach in this study by examining both brain tissue from individuals who had MS, alongside conducting an assessment of immune cells isolated from blood samples from people living with different subtypes of the disorder.

• Inflammasome genes are upregulated in the brains of people with primary progressive MS, but not secondary progressive MS. This is particularly evident in active lesions in the brain.
• Immune cells isolated from people with MS are particularly reactive in terms of NLRP3 activation.
• Immune cells isolated from people with MS secrete higher levels of the inflammatory cytokine interleukin‑1β, which is closely associated with NLRP3 activation, when compared to immune cells from healthy volunteers.
• The research suggests that the expression of NLRP3 inflammasome components is dysregulated in MS, both in the brain and in immune cells.

This work was led by Almudena Otálora-Alcaraz (PhD researcher) and Dr Eric Downer from the Discipline of Physiology in Trinity. Collaborators included clinicians from St. James’s Hospital and Beaumont Hospital in Dublin.

Speaking on the research, Dr Eric Downer, Associate Professor and Associate Director of Research, School of Medicine, Trinity College and lead author said:

“This work builds on previous research from my lab demonstrating the role of innate immune inflammation in MS. We took the approach of assessing the NLRP3 inflammasome both centrally and peripherally in MS, by employing the use of brain tissue samples and immune cells. Overall, we believe that our research further highlights that the NLRP3 inflammasome warrants full investigation in MS and may be a promising potential target for future MS therapies.”

This research matters because importantly, the NLRP3 inflammasome has been implicated in the pathogenesis of several disorders, including MS, with data suggesting that targeting the NLRP3 inflammasome has therapeutic efficacy across a range of disorders.

This is a translational study using only samples from human subjects, hence it sheds light on the importance of the NLRP3 inflammasome in a disease context, particularly MS. The study suggests that further attention should be given to the role of this signalling hub in MS development.

Almudena Otálora-Alcaraz, PhD researcher, said:

 “Our findings provide new insight into the role of the NLRP3 inflammasome in multiple sclerosis pathogenesis, highlighting inflammation as a potential key driver of disease progression. This improved understanding of disease-related inflammatory processes across different stages of MS could help guide the development of more targeted and effective treatments for people living with MS.”

Next steps for this research

The next step is to test the effectiveness of current and new therapeutics in targeting the NLRP3 inflammasome using immune cells from people with MS. This research is currently underway in the Downer lab in the Discipline of Physiology.

This work has been supported by the Irish Research Council Enterprise Partnership Scheme co-funded by Transpharmation Limited, and the Provosts PhD Project Awards at Trinity College Dublin. The researchers thank all study participants who were involved in the study, without whom this patient-focused research would be impossible to perform.

Read: You can read a full copy of the paper: ‘Elevated expression of the NLRP3 inflammasome in post-mortem brain white matter and immune cells in multiple sclerosis’ at this link  https://www.msard-journal.com/article/S2211-0348(26)00076-3/fulltext

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