Exploiting Rational Assembly to Map Distinct Roles of Regulatory Cues during Autoimmune Therapy

Autoimmune diseases like multiple sclerosis (MS), type 1 diabetes, and lupus occur when the immune system attacks host tissue. Immunotherapies that promote selective tolerance without suppressing normal immune function are of tremendous interest. Here, nanotechnology was used for rational assembly of peptides and modulatory immune cues into immune complexes. Complexes containing self-peptides and regulatory nucleic acids reverse established paralysis in a preclinical MS model. Importantly, mice responding to immunotherapy maintain healthy, antigen-specific B and T cell responses during a foreign antigen challenge. A therapeutic library isolating specific components reveals that regulatory nucleic acids suppress inflammatory genes in innate immune cells, while disease-matched peptide sequences control specificity of tolerance. Distinct gene expression profiles in cells and animals are associated with the immune signals administered in particulate and soluble forms, highlighting the impact of biophysical presentation of signals. This work provides insight into the rational manipulation of immune signaling to drive tolerance.

Automated summary

This study utilized nanotechnology to create immune complexes containing self-peptides and regulatory nucleic acids, which successfully reversed established paralysis in a preclinical MS model. Through a therapeutic library isolating specific components, it was found that regulatory nucleic acids suppress inflammatory genes, while disease-matched peptide sequences control specificity of tolerance.Distinct gene expression profiles were associated with the immune signals administered in particulate and soluble forms, indicating the importance of biophysical presentation of signals in driving tolerance.