Sensitisation via the skin plays a central role in the development of food allergy. Infants with skin barrier defect and atopic dermatitis (AD) show increased risk for sensitisation, food allergy, and other allergic co-morbidities. It remains largely unknown, if the sensitisation process itself can drive changes in the systemic immune system. Here we studied changes in skin and systemic T cell phenotypes during cutaneous sensitisation to enzyme hydrolysed gluten (E Glu) proteins in the absence or presence of AD-like skin inflammation in a Brown Norway rat model of food allergy.

AD-like skin inflammation was induced by the application of vitamin D3 analogue MC903 to shaved abdominal skin. E Glu was applied to normal or AD-inflamed abdominal skin for 1 hour, 3 times/week for 5 weeks, whereas control animals received PBS to normal skin. Allergic sensitisation was assessed by measurements of E Glu-specific IgE in serum, ear swelling test (EST), and clinical symptoms after oral challenge with E Glu. T cell phenotypes were analysed in the skin, blood, Peyer's patches, and mesentery lymph nodes (mLN) by flow cytometry. 

E Glu induced sensitisation when applied to normal skin. The sensitisation was associated with an increased EST response and clinical symptoms following oral challenge compared to control animals. Application of E Glu to AD-inflamed skin increased E Glu-specific IgE levels, the EST response, and clinical symptoms compared to animals sensitised through normal skin. Sensitisation through normal skin was associated with increased expression of the CD25 activation marker on skin cytotoxic T cells, whereas sensitisation through AD-inflamed skin was associated with CD25 expression on helper T cells. Sensitisation, irrespectively of normal or AD-inflamed skin, was associated with increased frequencies of skin regulatory (CD4⁺CD25⁺FoxP3⁺) T cells, which were of the Helios⁺ phenotype. Furthermore, sensitisation was associated with changes in the composition of CD103-, CD161- and MHC-II-, but not CCR4- or CCR9-expressing T cells in the blood, and with increased frequencies of CCR9-expressing T cells in the mLN.

Immune activation in response to skin sensitisation may be different in the context of normal and AD-inflamed skin. Systemic immune function may be affected by skin sensitisation even in the absence of AD. The role of systemic effects of skin sensitisation in food allergy and related allergic co-morbidities warrants further investigation.