# Engineering the Skin Microenvironment to Promote Allergen Tolerance

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $608,085

## Abstract

ABSTRACT
Allergic contact dermatitis (ACD) is a destructive T-cell-mediated inflammation of the skin,
resulting from repeated contact with allergens (e.g. nickel or poison ivy). ACD is one of the most
common skin diseases, afflicting roughly 15-20 percent of the population, with annual costs in
excess of $2 billion in the U.S. alone. Aside from avoiding known allergens when possible, current
treatments involve non-specific anti-inflammatories that transiently suppress cutaneous
inflammation, but fail to address the underlying immune dysfunction. In contrast, our bodies
ordinarily employ highly specific mechanisms to suppress excessive inflammation, many of which
are mediated by regulatory T cells (Tregs). Studies have shown that enhancing allergen or
autoantigen-specific populations of Tregs can promote tolerance, or hyporesponsiveness, and
ameliorate tissue-destructive inflammation. Information present in the local microenvironments
where dendritic cells encounter or present allergen dictates whether T cells will become
inflammatory effector T cells (Teff) or protective Tregs.
 The goal of the studies we propose is to develop an antigen specific strategy to prevent
and treat contact dermatitis. We recently demonstrated that sustained local delivery of TReg-
Inducing (“TRI”) factors and allergens with degradable, polymeric microparticles (MPs) or
microneedle arrays (MNAs) expands allergen-specific Tregs and inhibits Teff differentiation
during cutaneous allergen exposure, thereby promoting allergen-specific tolerance. In this
proposal, we will induce tolerance by engineering local skin or lymph node microenvironments to
promote Treg differentiation. To that end, we will leverage our multidisciplinary team’s combined
experience and capabilities to specifically deliver Treg-inducing factors to defined
microenvironments of the skin or skin draining lymph nodes using microneedle arrays and micro-
sized controlled release systems. Importantly, our experiments include translational studies
focusing on human skin that are designed to enable rapid translation of this strategy to clinical
trials.

## Key facts

- **NIH application ID:** 9964715
- **Project number:** 5R01AR074285-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Louis D Falo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $608,085
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964715

## Citation

> US National Institutes of Health, RePORTER application 9964715, Engineering the Skin Microenvironment to Promote Allergen Tolerance (5R01AR074285-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9964715. Licensed CC0.

---

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