Equine keratinocytes in the pathogenesis of insect bite hypersensitivity: Just another brick in the wall?

The research study focuses on understanding the role of equine keratinocytes in the development of insect bite hypersensitivity (IBH), a common skin disease in horses. The study explores the genetic changes in keratinocytes when exposed to allergens, investigating their role in the immune response and potential contribution to IBH.

Methods and Experimentation

• For the experiment, researchers used keratinocytes obtained from 9 horses affected with IBH, and 9 healthy horses. These were stimulated with Culicoides recombinant allergens and extract, allergic cytokine milieu (ACM) and a Toll-like receptor ligand 1/2 (TLR-1/2-L), all of which are relevant to the study of IBH.
• Using these standards, an investigation of their transcriptomes (the sum total of all the messenger RNA molecules expressed from the genes of an organism) helped comprehend the genetic activity in response to the stimuli.

Findings

• No transcriptional changes in keratinocytes were noted when exposed to the Culicoides allergens.
• Significant gene expression changes were observed when keratinocytes were stimulated with the allergic cytokine milieu. This included upregulation of genes encoding for specific chemokines like CCL5, -11, -20, -27 and interleukins such as IL31.
• Further noteworthy was the strong downregulation of genes such as SCEL and KRT16, which are involved in the formation of the epithelial barrier, an important protective feature of the skin.
• When keratinocytes were stimulated with TLR-1/2-L, they significantly upregulated expression of genes affecting Toll like receptor and NOD-receptor signaling pathway and NF-kappa B signaling pathway, among others.
• The transcriptomes of IBH affected and healthy horses, in most situations, were found to be very similar. Only a few differentially expressed genes were identified following stimulation with the allergic cytokine milieu and TLR-1/2-L.

Inference and Conclusion

• The data suggests that keratinocytes contribute to the innate immune response in horses.
• These cells are able to react significantly to different stimuli presented in the experiment, indicating a potential role in the pathogenesis of IBH.
• However, the similarity in gene response between keratinocytes from IBH affected and healthy horses indicates that the pathogenesis of IBH is likely far more complex than having just keratinocytes as the primary influencing factor.