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

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.

March to the beat of adaptive immunity

“…[17][18][19] Flg ft/ft mice have attenuated profilaggrin expression in the epidermis and absent functional filaggrin monomer (see Fig E2 in this article's Online Repository at www.jacionline.org), which is similar to what is seen in FLG-null patients. 5 As neonates, Flg ft/ft mice spontaneously have marked ichthyosis-like dermatitis with edema, erythema, hyperlinearity, and scaling compared with WT control animals (Fig 1, A and B).…”

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis

“…Since the seminal work of the McLean Lab has underscored the importance of skin barrier abnormalities as an etiological factor in AD, we focused on the effects of coal tar on the epidermal biology of this disease (1, 3, 8). Our results reveal a key role of the AHR signaling pathway in breaching the vicious The immunopathogenesis of AD has been studied directly on patients or in animal models based on allergic immune responses (29)(30)(31). We have recently developed in vitro organotypic models for psoriasis and AD (18,19), and have shown that the application of genetic techniques in these models could be used to study epidermal aspects of diseases (32).…”

Epicutaneous Sensitization Results in IgE-Dependent Intestinal Mast Cell Expansion and Food Anaphylaxis

“…6 We used this model to investigate whether a robust IgE antibody is sufficient for oral anaphylaxis. WT BALB/c mice were orally immunized with OVA+CT or CT alone, as a negative control, by weekly gavage for 8 weeks, then orally challenged with OVA (Fig.…”

“…6,45 We previously reported that mechanical injury caused by tape stripping induces TSLP production in the skin, and that DCs derived from skin injured by tape stripping are programmed by TSLP to drive a Th2 response and migrate to MLN. 46 TSLP levels were elevated levels in EC sensitized skin (Fig.…”

“…Fold induction of IL-4 gene expression was calculated using the comparative method for relative quantitation by normalization to the internal control β2-microglobulin, as described previously. 6 …”