# Immunomodulatory mechanisms of E-FABP in psoriasis pathogenesis

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $386,392

## Abstract

Summary
Psoriasis is the most prevalent and intractable immune-mediated chronic inflammatory skin disease. It is clear
that dendritic cells (DCs) and keratinocytes in the skin tissues play a central role in the pathogenesis of
psoriasis. The objectives of this proposal are to determine the role of epidermal fatty acid binding protein (E-
FABP) in promoting psoriasis pathogenesis through simultaneously targeting both DCs and keratinocytes and
in linking obesity-associated psoriasis development. E-FABP, first cloned in psoriatic skin tissues (also known
as psoriasis associated FABP), has been identified as a critical regulator of both metabolic and inflammatory
pathways. Our preliminary studies demonstrate that E-FABP is greatly upregulated in the skin tissue from
patients with psoriasis. Intriguingly, deficiency of E-FABP confers protection from imiquimod (IMQ) or IL-23-
induced psoriasis-like inflammation in mouse models. While obesity is associated with increased severity of
psoriasis and poor responses to therapy, the underlying mechanisms between obesity and psoriasis are
unknown. While high fat diet (HFD) increases E-FABP expression in both DCs and keratinocytes and promotes
obesity-associated chronic skin inflammation in wild type mice, E-FABP deficiency protects mice against HFD-
induced effects. All these data suggest that E-FABP may link obesity and psoriasis via regulating metabolism
and function of DCs and keratinocytes. Thus, we hypothesize that E-FABP, as a new link underlying the
obesity-psoriasis association, promotes psoriasis pathogenesis through enhancing cellular metabolism and
function of both DCs and keratinocytes. Therefore, targeting E-FABP may represent a novel strategy for
psoriasis therapy. We design three specific aims (Figure A) to address our hypotheses. Specific Aim 1 will
address how E-FABP regulates DC metabolism and function in psoriasis. We hypothesize that E-FABP links
FA metabolism and innate immune signaling in DCs and bridges innate and adaptive immune responses for
psoriasis pathogenesis. Specific Aim 2 will determine how E-FABP promotes keratinocyte aberrant
metabolism and differentiation in psoriasis. We will design experiments to test the hypothesis that E-FABP
expression in keratinocytes mediates innate signal-induced metabolic changes that are critical for abnormal
keratinocyte differentiation. Specific Aim 3 will examine whether E-FABP links the obesity/psoriasis
association using our unique E-FABP global and conditional knock out mouse models and samples from
psoriasis patients. In summary, this proposal will demonstrate a novel mechanism by which E-FABP promotes
psoriasis pathogenesis and links obesity-associated psoriasis development. Thus, targeting E-FABP may offer
a novel strategy for treatment of psoriasis and other inflammatory skin disorders.

## Key facts

- **NIH application ID:** 10459902
- **Project number:** 7R01AI137324-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Bing Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,392
- **Award type:** 7
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459902

## Citation

> US National Institutes of Health, RePORTER application 10459902, Immunomodulatory mechanisms of E-FABP in psoriasis pathogenesis (7R01AI137324-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10459902. Licensed CC0.

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