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

Cvitas, Iva; Oberhänsli, Simone; Leeb, Tosso; Dettwiler, Martina; Müller, Eliane; Bruggmann, Rémy; Marti, Eliane Isabelle (2020). Investigating the epithelial barrier and immune signatures in the pathogenesis of equine insect bite hypersensitivity. PLoS ONE, 15(4), e0232189. Public Library of Science 10.1371/journal.pone.0232189

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Insect bite hypersensitivity (IBH) is a Th-2, IgE-mediated dermatitis of horses caused by bites of insects of the genus Culicoides that has common features with human atopic dermatitis. Together with Th-2 cells, the epithelial barrier plays an important role in development of type I hypersensitivities. In order to elucidate the role of the epithelial barrier and of the skin immune response in IBH we studied the transcriptome of lesional whole skin of IBH-horses (IBH-LE; n = 9) in comparison to non-lesional skin (IBH-NL; n = 8) as well as to skin of healthy control horses (H; n = 9). To study the "baseline state" of the epithelial barrier, we investigated the transcriptome of non-lesional epidermis in IBH-horses (EPI-IBH-NL; n = 10) in comparison with healthy epidermis from controls (EPI-H; n = 9). IBH-LE skin displayed substantial transcriptomic difference compared to H. IBH-LE was characterized by a downregulation of genes involved in tight junction formation, alterations in keratins and substantial immune signature of both Th-1 and Th-2 types with particular upregulation of IL13, as well as involvement of the hypoxic pathway. IBH-NL shared a number of differentially expressed genes (DEGs) with IBH-LE, but was overall more similar to H skin. In the epidermis, genes involved in metabolism of epidermal lipids, pruritus development, as well as IL25, were significantly differentially expressed between EPI-IBH-NL and EPI-H. Taken together, our data suggests an impairment of the epithelial barrier in IBH-affected horses that may act as a predisposing factor for IBH development. Moreover, these new mechanisms could potentially be used as future therapeutic targets. Importantly, many transcriptional features of equine IBH skin are shared with human atopic dermatitis, confirming equine IBH as a natural model of skin allergy.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pathologie > Forschungsgruppe Dermatologie
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
08 Faculty of Science > Department of Biology > Bioinformatics

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Cvitas, Iva; Oberhänsli, Simone; Leeb, Tosso; Dettwiler, Martina Andrea; Müller, Eliane Jasmine; Bruggmann, Rémy and Marti, Eliane Isabelle

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

01 May 2020 11:42

Last Modified:

03 May 2020 02:42

Publisher DOI:

10.1371/journal.pone.0232189

PubMed ID:

32343720

BORIS DOI:

10.7892/boris.143780

URI:

https://boris.unibe.ch/id/eprint/143780

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