Low Threshold for Cutaneous Allergen Sensitization but No Spontaneous Dermatitis or Atopy in FLG-Deficient Mice

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Loss of FLG causes ichthyosis vulgaris. Reduced FLG expression compromises epidermal barrier function and is associated with atopic dermatitis, allergy, and asthma. The flaky tail mouse harbors two mutations that affect the skin barrier, Flgft, resulting in hypomorphic FLG expression, and Tmem79ma, inactivating TMEM79. Mice defective only for TMEM79 featured dermatitis and systemic atopy, but also Flgft/ft BALB/c congenic mice developed eczema, high IgE, and spontaneous asthma, suggesting that FLG protects from atopy. In contrast, a targeted Flg-knockout mutation backcrossed to BALB/c did not result in dermatitis or atopy. To resolve this discrepancy, we generated FLG-deficient mice on pure BALB/c background by inactivating Flg in BALB/c embryos. These mice feature an ichthyosis phenotype, barrier defect, and facilitated percutaneous sensitization. However, they do not develop dermatitis or atopy. Whole-genome sequencing of the atopic Flgft BALB/c congenics revealed that they were homozygous for the atopy-causing Tmem79matted mutation. In summary, we show that FLG deficiency does not cause atopy in mice, in line with lack of atopic disease in a fraction of patients with ichthyosis vulgaris carrying two Flg null alleles. However, the absence of FLG likely promotes and modulates dermatitis caused by other genetic barrier defects.

Details

OriginalspracheEnglisch
Seiten (von - bis)2611-2619.e2
Seitenumfang9
FachzeitschriftJournal of investigative dermatology
Jahrgang141
Ausgabenummer11
PublikationsstatusVeröffentlicht - Nov. 2021
Peer-Review-StatusJa

Externe IDs

Scopus 85108996893
PubMed 33894197
ORCID /0000-0003-4820-2560/work/142251099
ORCID /0000-0002-8134-5929/work/142257678

Schlagworte

Schlagwörter

  • Allergens/immunology, Animals, Dermatitis, Atopic/etiology, Female, Filaggrin Proteins/deficiency, Hypersensitivity/etiology, Ichthyosis Vulgaris/etiology, Mice, Mice, Inbred BALB C, Microbiota, Skin/immunology, Whole Genome Sequencing

Bibliotheksschlagworte