Active immunization using a single dose immunotherapeutic abates established EAE via IL-10 and regulatory T cells

Area of Science:

• Immunology
• Autoimmunity
• Tolerogenesis

Background:

• Inducing antigen-specific regulatory T cells (Treg) is crucial for resolving autoimmune diseases.
• Conventional Treg induction methods often involve disease induction or infection.
• Reovirus adhesin protein σ1 (pσ1) can facilitate tolerance when fused to a tolerogen.

Purpose of the Study:

• To investigate if myelin oligodendrocyte glycoprotein fused to pσ1 (MOG-pσ1) can stimulate antigen-specific Treg.
• To evaluate MOG-pσ1's efficacy in preventing and treating experimental autoimmune encephalomyelitis (EAE).

Main Methods:

• C57BL/6 mice were treated nasally with MOG-pσ1.
• Immune responses, including MOG-specific antibodies and delayed-type hypersensitivity (DTH), were assessed.
• EAE induction and therapeutic intervention with MOG-pσ1 were performed.
• Interleukin (IL) production by CD4+ T cells was analyzed.

Main Results:

• Nasal MOG-pσ1 treatment prevented EAE development and suppressed MOG-specific antibody and DTH responses.
• Resistance to EAE was mediated by Foxp3(+) Treg and Th2 cells, dependent on IL-10.
• MOG-pσ1 demonstrated rapid therapeutic effects in diminishing EAE, outperforming rMOG, pσ1, or pσ1+rMOG.
• MOG-pσ1 treatment led to increased IL-4, IL-10, and IL-28 production, unlike control groups.

Conclusions:

• MOG-pσ1 is a feasible platform for inducing antigen-specific tolerance.
• The pσ1 fusion strategy holds potential as an immunotherapeutic for autoimmune conditions.
• Ag-specific pσ1-based therapeutics are important for successful autoimmunity treatment.