How Helminths Help Despite Elevated IL-10 in Multiple Sclerosis (MS)

The Problem: Dysregulated IL-10 Production and Response in MS

The core problem with IL-10 in MS before helminth intervention is a dysregulation of IL-10 production and response, not simply its quantity. While elevated IL-10 levels are often detected in MS patients, these do not consistently translate into effective control of neuroinflammation or disease progression. Specialized IL-10-producing cells—particularly regulatory B cells (Bregs) and regulatory T cells (Tregs)—are often reduced in number or impaired in function in MS, compromising their ability to suppress pathogenic T cell subsets such as Th1 and Th17.

In addition, pro-inflammatory mediators like IL-6 are frequently elevated in MS and can interfere with IL-10 signaling pathways, inducing resistance to IL-10’s immune-suppressive effects. IL-10 produced by non-regulatory or inappropriate immune cells, or delivered at the wrong time, may even exacerbate disease by promoting survival of harmful lymphocytes. This complex regulatory imbalance means that the immune system remains skewed towards inflammation despite measurable IL-10, contributing to ongoing demyelination, neurodegeneration, and clinical symptoms.

This systemic imbalance in IL-10 biology represents a major therapeutic challenge, as attempts to increase IL-10 levels alone have yielded mixed and often disappointing results in MS treatment.

The Role of Regulatory B Cells and Their Dysfunction in MS

A crucial piece of this imbalance lies in the dysfunction of IL-10-producing regulatory B cells, also known as B10 cells. These cells play key roles in immune tolerance by secreting IL-10 and additional regulatory factors that suppress autoreactive T cells and promote tissue protection. In MS, B10 cells are often defective, leading to insufficient IL-10-mediated regulation.

Restoring the number and function of these Bregs is thus critical to re-establishing immune balance. This is where helminth infections bring a distinct advantage: they robustly expand and activate these IL-10-producing regulatory B cells, enabling a more effective anti-inflammatory and neuroprotective response than the native system can achieve alone.

How Helminths Restore Immune Balance in MS

Helminths induce a coordinated, multifaceted immune regulatory network that addresses the systemic IL-10 imbalance via multiple mechanisms:

Induction and Expansion of Functional IL-10-Producing Regulatory B Cells
Helminths stimulate the proliferation of CD19+ Bregs secreting IL-10 along with neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). This dual action suppresses autoimmune inflammation while directly supporting neural repair.
Broad Immune Modulation Through TLR2 Signaling
Parasite antigens upregulate Toll-like receptor 2 (TLR2) on B cells and dendritic cells, leading to MyD88- and ERK-dependent signaling that suppress pro-inflammatory cytokines (IL-1β, IL-6, IL-12, TNF-α) and simultaneously enhances IL-10 and TGF-β production, promoting immune tolerance.
Sustained Effects Require Persistent Helminth Exposure
Long-term studies show that continuous helminth infection maintains regulatory immune profiles and clinical stability in MS, with parasite clearance reversing benefits and triggering relapse, indicating the necessity of ongoing helminth-derived signals.
Activation of IL-10-Independent Regulatory Pathways
Helminths also engage the GAS6–TAM receptor axis (TYRO3, AXL, MERTK), selectively restraining pathogenic Th17 cells, adding a complementary layer of immune regulation independent from IL-10 effects.
Promotion of Trained Immunity and Balanced Regulatory Responses
The helminth-induced environment favors Th2 polarization, regulatory T cell expansion, immunoregulatory monocytes, and microbiome alterations. This supports durable, systemic immune tolerance that minimizes tissue damage.

Supporting Evidence

Regulatory B Cell Function: Helminth-infected MS patients exhibit higher frequencies of IL-10+ regulatory B cells producing neurotrophic factors, enhancing anti-inflammatory and neuroprotective responses.
Immune Signaling: Helminth exposure increases TLR2 expression and downstream signaling in immune cells, balancing cytokine profiles toward regulation.
Clinical Outcomes: Longitudinal studies correlate persistent helminth infections with reduced MS relapse rates and MRI activity; elimination of infection worsens disease.
Additional Regulatory Axes: GAS6–TAM receptor pathways activated by helminths dampen pathogenic Th17 responses independently of IL-10.
Trained Immunity: Wide-ranging systemic and microbiome effects further bolster immune tolerance.

Conclusion

Elevated IL-10 levels in MS patients mask a deeper systemic dysfunction involving dysregulated IL-10 production and impaired responsiveness. Helminths re-establish immune homeostasis not by simply increasing IL-10 quantity but by shaping a comprehensive, coordinated immune regulatory network that expands functional IL-10-producing regulatory B cells, activates complementary anti-inflammatory pathways, and fosters neuroprotection.

These insights offer a compelling model of MS immune regulation and a promising foundation for novel helminth-inspired therapeutic approaches.

Citations

Seeking Balance: Potentiation and Inhibition of Multiple Sclerosis – PMC
Under the influence: environmental factors as modulators – Frontiers
Decoding disease burden in multiple sclerosis – ScienceDirect
Dysregulation of IL-10 and IL-12p40 in secondary progressive – PubMed
Immune System Dysregulation in the Progression of Multiple Sclerosis – ScienceDirect

Tag: multiple sclerosis