SummaryBackground. Skin-resident memory T (T RM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore, the mechanisms whereby T RM cells induce rapid recall responses need further investigation. Objectives. To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. Methods. To address these questions, we analysed responses to contact allergens in mice and humans sensitized to 2,4-dinitrofluorobenzene and nickel, respectively. Results. Challenge responses in both mice and humans were dramatically increased at sites previously exposed to allergens as compared with previously unexposed sites. Importantly, the magnitude of the challenge response correlated with the epidermal accumulation of interleukin (IL)-17A-producing and interferon (IFN)--producing T RM cells. Moreover, IL-17A and IFN-enhanced allergen-induced IL-1 production in keratinocytes. Conclusions. We show that sensitization with contact allergens induces a strong, longlasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN--producing CD8 + T RM cells.
Background:The oxidase activity of human Ero1␣ generates hydrogen peroxide in the ER. Results: Overexpression of a hyperactive Ero1␣ mutant induces the unfolded protein response but does not cause a broad antioxidant response. Conclusion: Ero1␣ hyperactivity elicits ER stress through local ER lumenal hyperoxidation. Significance: These findings show how the cell negotiates oxidative stress generated specifically in the lumen of the ER.
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