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Epicutaneous challenge of orally immunized mice redirects antigen-specific gut-homing T cells to the skin
Michiko K. Oyoshi, … , James J. Campbell, Raif S. Geha
Michiko K. Oyoshi, … , James J. Campbell, Raif S. Geha
Published May 2, 2011
Citation Information: J Clin Invest. 2011;121(6):2210-2220. https://doi.org/10.1172/JCI43586.
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Research Article Immunology

Epicutaneous challenge of orally immunized mice redirects antigen-specific gut-homing T cells to the skin

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Abstract

Patients with atopic dermatitis (AD) often suffer from food allergy and develop flares upon skin contact with food allergens. However, it is unclear whether T cells sensitized to allergens in the gut promote this skin inflammation. To address this question, we orally immunized WT mice and mice lacking the skin-homing chemokine receptor Ccr4 (Ccr4–/– mice) with OVA and then challenged them epicutaneously with antigen. Allergic skin inflammation developed in the WT mice but not in the mutants and was characterized by epidermal thickening, dermal infiltration by eosinophils and CD4+ T cells, and upregulation of Th2 cytokines. T cells purified from mesenteric lymph nodes (MLNs) of orally immunized WT mice transferred allergic skin inflammation to naive recipients cutaneously challenged with antigen, but this effect was lost in T cells purified from Ccr4–/– mice. In addition, the ability of adoptively transferred OVA-activated T cells to home to the skin following cutaneous OVA challenge was ablated in mice that lacked lymph nodes. These results indicate that cutaneous exposure to food antigens can reprogram gut-homing effector T cells in LNs to express skin-homing receptors, eliciting skin lesions upon food allergen contact in orally sensitized AD patients.

Authors

Michiko K. Oyoshi, Abdallah Elkhal, Jordan E. Scott, Marc-Andre Wurbel, Jason L. Hornick, James J. Campbell, Raif S. Geha

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Figure 1

Dermal infiltrates and cytokine expression in EC-challenged skin of orally immunized BALB/c mice.

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Dermal infiltrates and cytokine expression in EC-challenged skin of oral...
(A) Representative photomicrographs of H&E sections from EC-challenged skin of orally sensitized mice with Sal/CT or OVA/CT. Scale bars: 10 μm. Arrows point to eosinophils. (B) Epidermal thickness. (C) Numbers per HPF of eosinophils and CD4+ cells infiltrating the dermis. (D) Relative cytokine mRNA expression. The mean for saline-challenged skin of saline immunized mice was arbitrarily set at 1. Values represent individual mice, and bars represent mean (n = 6–7 mice per group). Two-tailed Student’s t test was used to determine statistical differences between each set of 2 groups. Similar results were obtained in 2 other independent experiments with 4 mice per group.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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