0517 scRNA-seq identifies atopic dermatitis development marked by early neutrophils and T cell shifts in filaggrin-null mice with environmental sensitivity

Document Type

Conference Proceeding

Publication Date

8-1-2025

Publication Title

J Invest Dermatol

Abstract

Filaggrin (Flg) deficiency is a major risk factor for atopic dermatitis (AD) with epicutaneous sensitization and increased permeability shown in filaggrin-null (Flg-/-) mice. Flg loss-of-function variants are semipenetrant for AD suggesting a role for environmental effects. We hypothesize differential AD-like, skin inflammation induced by MC903 in Flg-/- adult mice housed in two different animal facilities. Flg-/- mice in facility A developed normally yet with increased Streptococcus dysbiosis and higher overall rate of MC903-induced inflammation but was not significant (vs. wild-type [wt] mice). Flg-/- mice in facility B exhibited a perinatal flaky tail that resolved yet with a significant increase in the overall rate of MC903-inflammation (p<0.05). Flow cytometry revealed neutrophil infiltration in the early (days 1-6) and not in the late phase (days 7-12) with notable TCRb+ cell influx in Flg-/- mice. scRNA-seq of treated ear skin further identified 22 distinct clusters and validated the observed increased neutrophils yet with additional myeloid and lymphoid immune cells in Flg-/- mice in the early and late phases, respectively. Tslp was specific to suprabasal KCs that persisted in both phases whereas IL2/CD101 T cells predominated the early phase and shifted to CD8+, Treg, and Th2 by the late phase with higher inflammation. In summary, our MC903 Flg-/- study identifies environmental sensitivity and longitudinal development of AD with early neutrophil infiltration and late T cell shifts that offers insights into potential therapeutic targets to modulate specific immune cell subsets in treating AD.

Volume

145

Issue

8

First Page

S89

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