# Filaggrin Expression in Atopic Dermatitis: Regulation and Impact on Disease Progression

> **NIH NIH U19** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $233,274

## Abstract

Abstract
Atopic dermatitis (AD) affects up to 20% of children worldwide and is an increasing public health problem.
Although AD in infants and young children can resolve, there is a substantial risk of progression from AD to other
atopic diseases, including food allergy (FA), allergic rhinitis, and asthma, i.e. the atopic march. The mechanisms
underlying the atopic march are incompletely understood and this is a critical gap in knowledge as this
information is necessary in order to design preventive strategies that can hijack or abort the atopic march. The
crucial role of Filament aggregating protein (or filaggrin, FLG) in the development of AD and the atopic march
has been demonstrated and extensively reviewed. The Mechanisms of Progression of Atopic Dermatitis to
Asthma in CHildren (MPAACH) cohort is an early life cohort of children with AD with extensive longitudinal clinical
health outcomes data and longitudinal biospecimens. Using MPAACH, we recently found that low non-lesional,
but not lesional, skin FLG expression is associated with the development of co-sensitization and moderate-
severe AD, both key risk factors for the future development of allergic co-morbidities of AD. Project 2 will test
the central hypothesis that genetic factors including CARD14 act in concert with environmental factors and
inflammation to determine FLG expression in AD skin, driving transient or persistent skin barrier dysfunction,
which may differentially impact long-term AD outcomes. Project 2 builds upon prior cycles of AADCRC funding
and leverages the extensive longitudinal clinical and molecular data and biospecimens available from MPAACH
and Project 1. In Aim 1, we will identify genetic variants that modulate skin FLG expression and integrate this
with clinical, exposure, and molecular data from MPAACH to identify the combination of factors that determine
skin FLG expression. We found that rs11652075 in CARD14 results in increased expression of CARD14 and
leads to attenuated FLG expression. In Aim 2, we will build on this data and determine the mechanisms that link
rs11652075 and enhanced CARD14 signaling to FLG homeostasis. While LoF FLG mutations are important in
the atopic march, the relationship between the trajectory of FLG expression in early life and over time with
longitudinal AD outcomes is unclear. In Aim 3, we will determine the impact of low skin FLG expression
(persistent or transient) over time and the genetic loci identified in Aim 1 on AD outcomes. Based on reports that
early application of emollients to the skin may prevent the development of AD, allergic sensitization, and food
allergy, this study is clinically important because it may help identify individuals with the magnitude and duration
of dysregulated barrier function that may benefit from prevention and intervention strategies designed to enhance
skin barrier function. Moreover, our study will help determine the optimal timing to deliver these interventions.
Finally, this project ad...

## Key facts

- **NIH application ID:** 10260728
- **Project number:** 2U19AI070235-16
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Leah Claire Kottyan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $233,274
- **Award type:** 2
- **Project period:** 2006-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260728

## Citation

> US National Institutes of Health, RePORTER application 10260728, Filaggrin Expression in Atopic Dermatitis: Regulation and Impact on Disease Progression (2U19AI070235-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10260728. Licensed CC0.

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