New insights into the skin immune response in nickel allergy

Researchers from the LEO Foundation Skin Immunology Research Center (SIC) at the University of Copenhagen, in collaboration with the Department of Dermatology and Allergy at Copenhagen University Hospital, Herlev and Gentofte, and with support from the Bio Research and Innovation Centre have made new insights into how the immune system reacts to repeated nickel exposure in individuals with nickel allergy.

The study reveals how epidermal T cell responses evolve when previously allergen-exposed skin is challenged multiple times with nickel.

Nickel-allergic participants were patch-tested with nickel on the same skin site three times, with 21 days between each exposure. "With each exposure, we observed that the clinical response became more severe", explained Dr. Kelvin Yeung, the first author on this study.

To explore the immune response at the nickel-exposed site in depth, the researchers took biopsies of the skin three weeks after nickel exposure and analyzed them with state-of-the-art technologies: flow cytometry and single-cell RNA sequencing.

"We found that T cells in the skin epidermis were tissue-resident memory T (T_RM) cells, which can reside in the skin for long periods of time. With each nickel exposure, the number of CD4⁺ and CD8⁺ T cells increased. Distinct T cell populations were identified, including Th2- and Th17-like CD4⁺ T_RM cells as well as cytotoxic CD8⁺ T_RM cells.

We noticed that individuals could generate quite distinct responses, and that all participants also exhibited a polyclonal population of regulatory T cells, suggestive of ongoing attempts by the immune system to restrain inflammation."

Together, these findings highlight the heterogeneous and dynamic nature of epidermal T cell responses in nickel allergy following repeated contact allergen exposure. The study underscores the importance of minimizing repeated contact with nickel in sensitized individuals and suggests that personalized therapeutic strategies may be required for patients with severe or persistent disease.

By showing how local immune memory in the skin is reinforced over time, this work provides a valuable framework for developing more targeted interventions.

Read the full study: British Journal of Dermatology
DOI: 10.1093/bjd/ljaf427