Sensitization via Healthy Skin Programs Th2 Responses in Individuals with Atopic Dermatitis

Abstract

Allergen-specific responses in atopic dermatitis (AD) are skewed toward a Th2 profile. However, individuals with AD have been shown to make effective virus-specific Th1 responses, raising the possibility that the skin itself contributes to driving the AD Th2 immunophenotype. Therefore, to explore the programming of immunological sensitization by the skin, we examined the outcome of sensitization through non-lesional skin of individuals with AD and healthy controls. Volunteers (controls, AD individuals with filaggrin gene (FLG) mutations (ADFM), and AD individuals without FLG mutations (ADWT)) were sensitized by cutaneous application of 2,4-dinitrochlorobenzene (DNCB), a small, highly lipophilic chemical sensitizer. At the doses tested, DNCB showed equal penetration into skin of all groups. Clinical reactions to DNCB were significantly reduced in AD. Although both controls and AD made systemic DNCB-specific Th1 responses, these were reduced in AD and associated with significantly Th2-skewed DNCB-specific T-cell responses. Th2 skewing was seen in both ADFM and ADWT, with no difference between these groups. After 3 months, DNCB-specific Th2 responses were persistent in individuals with AD, and Th1 responses persisted in controls. These data provide evidence that when antigen penetration is not limiting, AD skin has a specific propensity to Th2 programming, suggesting the existence of altered skin immune signaling that is AD-specific and independent of FLG status.

Inflamed skin predisposes to sensitization to less potent allergens

“…The Th1 response to this allergen is of shorter duration in patients with atopic dermatitis compared with healthy control subjects, and in fact disappears within a few months of sensitization in the majority, but it does persist for months in a substantial minority of patients with atopic dermatitis. 9 This confirms that patients with atopic dermatitis can be sensitized and a substantial minority of patients retains delayed-type hypersensitivity even to a potent allergen.…”

iPad—Increasing Nickel Exposure in Children

“…The exact prevalence of ACD in patients with AD remains unclear, as T helper 2 axis flare inhibition may affect patch test reproducibility. 11 As has been reported by other authors, 12,13 our patient' s 1+ reaction to nickel was a significant finding in association with a flare of his generalized dermatitis. By detecting a relevant allergen and controlling his nickel exposure sources, the patient had significant clinical improvement and has remained in remission for 5 months.…”

Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin

“…The T H 2-polarized responses were independent of filaggrin (FLG) mutation status, 27 which is consistent with the lack of association between ACD and FLG mutations in most studies. 26,28,29 Past studies did not address the role of AD skin phenotype in influencing cutaneous allergic responses. We have shown recently that different allergens induce differential immune polarization, showing T H 2 and T H 22 skewing with fragrance, 30 which might explain the higher prevalence of ACD to fragrances in patients with AD.…”