Update on canine filaggrin: a review

Abstract

Human filaggrin (FLG) plays a key role in epidermal barrier function, and loss-of-function mutations of its gene are primarily responsible for the development of human atopic dermatitis (AD). FLG expression is also reduced in the epidermis of atopic patients, due to the transcriptional effect of Th2 type cytokines. Canine atopic dermatitis (CAD) is a prevalent skin disease that shares many clinical and pathogenic features with its human homologue. The aim of this review is discuss current knowledge on canine filaggrin (Flg) in both healthy and atopic dogs, as compared to the human protein. Although the molecular structures of the two proteins, as deduced from the sequences of their gene, are different, their sites of expression and their proteolytic processing in the normal epidermis are similar. Concerning the expression of Flg in CAD, conflicting results have been published at the mRNA level and little accurate information is available at the protein level. It derives from a large precursor, named profilaggrin (proFLG), formed by several FLG units and stored in keratohyalin granules of the stratum granulosum. Canine and human proFLG sequences display little amino acid similarity (33% as shown using the Basic Local Alignment Search Tool (BLAST)) except at the level of the S100 homologous part of the N-terminus (75%). Genetic studies in the dog are at an early stage and are limited by the variety of breeds and the small number of cases included. Many questions remain unanswered about the involvement of Flg in CAD pathogenesis.

Transient and reversible reduction of stratum corneum filaggrin degradation products after allergen challenge in experimentally mite‐sensitised atopic dogs

“…That a skin barrier dysfunction in canine natural (i.e. spontaneous) AD also exists is now beyond controversy; the various anomalies have been summarised in several reviews on this topic 8–11 . At this time, however, we could not find any evidence for mutations in FLG — or for that matter, in any gene encoding proteins involved in skin barrier function — to be convincingly associated with AD in any canine breed.…”

“…As discussed in the introduction to this paper, the dysfunction of the epidermal barrier in atopic dogs is firmly established. [8][9][10][11] However, the controversy arises whether this barrier dysfunction is a primary (genetic) defectone that might need a therapeutic correctionor one simply resulting from the underlying allergic inflammation (i.e. a secondary deficiency).…”

Atopic Dermatitis in Domestic Animals: What Our Current Understanding Is and How This Applies to Clinical Practice

“…Filaggrin mutations have been reported as one of the most documented risk factors for atopic dermatitis in people [ 37 , 38 ]; thus, it was natural to address this issue in dogs. We now know that more than one filaggrin-type protein exists in dogs, although the exact function of filaggrin 2 in dogs is not clear [ 39 ]. Both filaggrin-type proteins are expressed in the upper layers of the skin and play a role in the differentiation of the epidermis and in the hydration of the skin.…”

Epithelial–immune crosstalk with the skin microbiota in homeostasis and atopic dermatitis – a mini review

“…These results suggest a close association between activated type 2 immunity, FLG deficiency and S. aureus colonisation in AD pathogenesis. Although the expression of Flg gene and FLG protein in healthy dogs are well‐characterised, 35,36 the results of the mRNA and protein expression in canine AD are inconsistent among the studies 37 . Further research on FLG in canine AD, including testing antibodies specifically detecting the canine FLG, is needed.…”