Investigating the epithelial barrier and immune signatures in the pathogenesis of equine insect bite hypersensitivity.

The research investigates the role of the epithelial barrier and skin immune response in equine Insect Bite Hypersensitivity (IBH), a dermatitis in horses caused by insect bites that is akin to human atopic dermatitis. Differences were found in the gene expression of horses affected by IBH, suggesting compromised epithelial barriers, which may be contributing to the onset of IBH. The study also suggests that these new findings could prove beneficial as therapeutic targets, and equine IBH could serve as a model for studying skin allergies.

Investigation of the Epithelial Barrier

• The researchers were specifically interested in understanding the role of the epithelial barrier – tissues that form the outer layer of an organism – in the development of IBH. To do this, they compared the transcriptome, or the total collection of transcripts in a cell, of the skin of horses with IBH to those without.
• Both lesional (IBH-LE) and non-lesional (IBH-NL) skin of horses with IBH were examined and compared with skin from healthy horses. Additionally, to understand the ‘baseline state’ of the epithelial barrier, the study compared the transcriptome of the non-lesional epidermis of horses with IBH with the healthy epidermis of control horses.
• Differences were observed in the transcriptomics of the IBH-affected skin compared to healthy skin. There were notable reductions in genes involved in the formation of tight junctions (crucial for maintaining a robust epithelial barrier), alterations in keratins (proteins vital for skin structure and function), and a significant immune response with evidence of both Th-1 and Th-2 type immune responses.
• The study also revealed an impact on the hypoxic pathway, a key physiological progression characterized by a reduction in tissue oxygen levels which can modulate various cellular functions.

Identifying Differences in Skin Immune Response and Potential Therapeutic Targets

• While non-lesional skin from IBH-affected horses shared some differences with lesional skin, it was overall more similar to healthy skin. The study identified a differential expression of genes related to the metabolism of epidermal lipids and the development of pruritus (itching), marking key differences in the skin immune response.
• Based on these findings, the researchers suggested an impairment of the epithelial barrier in IBH-affected horses, making them more susceptible to IBH. These identified differences offer potential new therapeutic targets for treating the disease.

Equine IBH as a Model for Skin Allergies

• The study also pointed out the shared transcriptional features between equine IBH and human atopic dermatitis, a common inflammatory skin condition. This finding suggests that equine IBH could serve as a natural model for studying and understanding skin allergies, contributing to the development of treatments for both animals and humans that are affected by atopic dermatitis.