Researchers delve into the skin of horses affected by Insect Bite Hypersensitivity

African Horse Sickness is spread by the Culicoides (midges) species. A 16th-inch-long (1.6mm) female biting midge (Culicoides sonorensis) feeding on blood.
Culicoides (midges) species. Pictured is a 16th-inch-long (1.6mm) female biting midge (Culicoides sonorensis) feeding on blood. © Scott Bauer, USDA ARS

Gene-driven differences identified in the skin in horses appear to be a factor in Insect Bite Hypersensitivity (IBH), researchers report.

IBH is the most common allergic skin disease affecting horses.

Triggered by Culicoides biting midges, it is seasonally recurrent and results in a very itchy form of dermatitis. Lesions that develop will often worsen as the horse rubs, becoming crusty, exuding dandruff, and losing hair.

IBH has overlapping features with human atopic dermatitis, Iva Cvitas and her colleagues at the University of Bern in Switzerland noted in the journal, PLOS ONE.

Several studies have characterized IBH as a type 1 Immunoglobulin E (IgE) dependent hypersensitivity. IgE is a type of antibody found only in mammals. It is known to have a pivotal role in responses to allergens.

Recent research suggests that defects in the epithelial barrier play an important role in the development of type 1 hypersensitivities in humans.

Although IBH is the most frequent type 1 allergic skin disease of horses, the role of the epithelial barrier and skin immune response in the progression of the condition has not been thoroughly studied.

The study team set out to understand the role of the epithelial barrier in the development of IBH, as well as to characterize the type of immune responses involved.

For their research, the study team examined the transcriptome — the sum total of all the messenger RNA molecules expressed from the genes — in IBH-affected skin from nine horses, comparing them to unaffected skin from the same horses. They similarly examined the skin of nine healthy control horses.

The skin with IBH lesions displayed substantial transcriptomic differences compared to the healthy controls.

Lesion-affected skin was characterized by a downregulation of genes involved in the all-important tight junction formation of the epithelial barrier, alterations in keratins, and there were substantial immune signatures of both Th-1 and Th-2 cell types, which are both involved in the immune response.

There was notable upregulation of the cytokine Interleukin 13 (IL13), which is usually released to fight inflammation, as well as strong involvement of the hypoxic pathway, which affects oxygen levels in the tissue.

Unaffected skin on the horses with IBH showed some similarities with lesion-affected skin, but was overall more similar to the skin of the healthy controls.

In the epidermis, genes involved in metabolism of epidermal lipids, development of itching, as well as the cytokine Interleukin-25 (IL-25) were differentially expressed between the healthy controls and the unaffected skin of horses affected by IBH.

Taken together, the findings suggest an impairment of the epithelial barrier in IBH-affected horses that may act as a predisposing factor for the development of the conditions, they said.

“These new mechanisms could potentially be used as future therapeutic targets.”

Many features of equine IBH skin are shared with human atopic dermatitis, confirming equine IBH as a natural model of skin allergy.

Discussing their findings, the researchers said: “Our data showed significant downregulation in the group of genes involved in the formation of tight junctions in the skin.”

The findings suggest that lesional skin of horses with IBH is characterized by alterations in adherens junctions – the protein complexes that occur at cell-to-cell junctions in epithelial and endothelial tissue.

New mechanisms identified in the study, such as immune-mediated alterations in the epithelial barrier and IL13 upregulation in lesion-affects skin, as well as lipid metabolism impairment in unaffected skin in IBH horses, are most probably important in the progression of IBH, they said.

These avenues could potentially be explored as new therapeutic targets, once their relevance is confirmed, the researcher said.

The study team comprised Cvitas, Simone Oberhänsli, Tosso Leeb, Martina Dettwiler, Eliane Müller, Remy Bruggman and Eliane Isabelle Marti.

Cvitas I, Oberhänsli S, Leeb T, Dettwiler M, Müller E, Bruggman R, et al. (2020) Investigating the epithelial barrier and immune signatures in the pathogenesis of equine insect bite hypersensitivity. PLoS ONE 15(4): e0232189.

The study, published under a Creative Commons License, can be read here

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