# Tunable Assembly of Regulatory Immune Signals to Promote Myelin-specific Tolerance

> **NIH VA I01** · BALTIMORE VA MEDICAL CENTER · 2020 · —

## Abstract

During autoimmunity, the body identifies and attacks “self” molecules as foreign. Current therapies employ broad
immunosuppression, which is beneficial to patients, but can leave them immunocompromised. This limitation,
along with the lack of cures, has sparked intense interest in strategies that could control autoimmunity with
vaccine-like specificity, leaving the rest of the immune system intact. Several pre-clinical reports and clinical trials
have investigated this theory to combat multiple sclerosis (MS), a neurodegenerative disease that impacts many
Veterans and occurs when myelin in the central nervous system (CNS) is attacked by the immune system. An
important finding from these studies is that co-administration of myelin peptide and tolerizing immune signals
can promote the development of regulatory T cells (TREGS) that ameliorate disease. Interestingly, one set of
pathways hindering control of myelin-driven inflammation are toll like receptors (TLRs). In healthy individuals,
these pathways detect pathogen-associated patterns to support innate immunity. However, recent studies reveal
that toll like receptor signaling – TLR9, for example – is elevated in human MS and in experimental autoimmune
encephalomyelitis (EAE), a mouse model of MS. Suppressing TLR9 function not only reduces inflammation, but
also promotes TREGS and improves disease. Polarization of naïve, myelin-reactive T cells into inflammatory T
cells (e.g., TH17) or TREGS is localized to spleen and lymph nodes (LNs), tissues that coordinate immunity. Thus,
strategies that help program how T cells differentiate when myelin is presented in LNs – for example, delivering
regulatory cues – could generate large populations of myelin-specific TREGS that stop pathogenic immune cells
without broad suppression. Nanotechnology holds great promise in this area through increased control over
targeting, release kinetics, and delivery of multiple signals. However, many polymer particles and other materials
exhibit intrinsic features that activate inflammatory pathways, which could exacerbate autoimmune disease.
Strategies that mimic attractive features of biomaterials, while eliminating inflammatory “carrier” effects could be
transformative for new therapies for MS or other autoimmune diseases. Toward this goal, the proposed research
will use polyionic immune signals to create novel nanostructured capsules built entirely from regulatory immune
signals and myelin antigens. These immune polyelectrolyte multilayers (“iPEMs”) are assembled through
electrostatic interactions on a template, which is then removed to leave vaccines capsules that juxtapose myelin
and TLR9-suppressive nucleic acids (GpG). Since there is no carrier, the density of signals in iPEMs is very high
relative to lipid or polymer formulations with cargo embedded in a matrix. Further, the particles condense the
signals at high densities, a characteristic that could promote differentiation toward TREG through co-localization
of m...

## Key facts

- **NIH application ID:** 9932291
- **Project number:** 5I01BX003690-04
- **Recipient organization:** BALTIMORE VA MEDICAL CENTER
- **Principal Investigator:** Christopher M Jewell
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932291

## Citation

> US National Institutes of Health, RePORTER application 9932291, Tunable Assembly of Regulatory Immune Signals to Promote Myelin-specific Tolerance (5I01BX003690-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9932291. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*