Cvitas, Iva; Galichet, Arnaud; Marti, Eliane Isabelle; Müller, Eliane Jasmine; Chu, Shui Ling (2020). Toll-like receptor-ligand induced thymic stromal lymphopoietin expression in primary equine keratinocytes. Veterinary dermatology, 31(2), pp. 154-162. Blackwell Science 10.1111/vde.12813
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BACKGROUND
Thymic stromal lymphopoietin (TSLP) plays a key role in the development of allergic inflammation. Little is known about possible triggers of equine TSLP expression.
HYPOTHESIS/OBJECTIVES
To investigate TSLP expression in equine insect bite hypersensitivity (IBH) skin lesions. The capacity of TLR 1-8 ligands (L) and of atopic cytokine milieu as potential triggers of TSLP and of interleukin (IL)-6 as a downstream effector molecule of TLR signalling, were examined in primary equine keratinocyte cultures.
ANIMALS
Lesional skin from IBH-affected and healthy skin from control-horses (n = 9 each group) was sampled.
METHODS AND MATERIALS
Keratinocyte cultures were established from six healthy horses and stimulated with TLR 1-8-L, and with IL-4 and tumor necrosis factor-α, to mimic an atopic inflammation cytokine milieu. TSLP and IL-6 gene expression was assessed by quantitative real-time PCR.
RESULTS
Expression of TSLP was significantly greater in IBH lesions compared to healthy skin. TLR 1-8-L significantly upregulated TSLP expression in keratinocytes. The strongest upregulation was induced by TLR 1/2-L and TLR 3-L. Combination of atopic cytokine milieu and TLR 1/2-L or TLR 3-L further increased TSLP expression. TLR-L 1-5 stimulation significantly upregulated IL-6 expression.
CONCLUSIONS AND CLINICAL IMPORTANCE
The data herein suggest that the upregulation of TSLP expression in lesional skin of IBH-affected horses might play a role in IBH development. Moreover, TSLP expression is induced by TLR-L, in particular by TLR 1/2-L and TLR 3-L, and is further increased by atopic cytokine milieu, indicating a mechanism for TSLP-mediated exacerbation of IBH.