Dupilumab-Associated Head and Neck Dermatitis Shows a Pronounced Type 22 Immune Signature Mediated by Oligoclonally Expanded T Cells

Author Type(s)

Student

Document Type

Abstract

Publication Date

8-2024

DOI

10.1016/j.jid.2024.06.811

Journal Title

Journal of Investigative Dermatology

Keywords

Humans, Antibodies, Monoclonal, T-Lymphocytes, Antibodies, Monoclonal, Humanized, Dermatitis, Atopic, Interleukin-13, Treatment Outcome, Severity of Illness Index

Abstract

Dupilumab, a therapeutic antibody blocking the eczematous type 2 immune response in atopic dermatitis (AD), has shown efficacy in many clinical trials and real-world observational studies. In addition to blepharitis and conjunctivitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients at any time after dupilumab initiation. Histopathological features distinct from conventional AD suggest a drug effect, but the exact underlying mechanisms remain unknown. We thus profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and compared data with untreated AD of the same region and of the trunk, as well as healthy control skin. We found that dupilumab treatment was accompanied by normalization of IL-4/IL-13 downstream activity markers such as CCL13, CCL17, CCL18 and CCL26, confirming effective type 2 inhibition within DAHND lesions. By contrast, we found strong increases in type 22-associated markers (IL22, AHR) especially in oligoclonally expanded T cells, accompanied by enhanced keratinocyte activation (S100A7, S100A8, S100A9) and IL-22 receptor upregulation, while expression of the IL22 inhibitor IL22RA2 (IL-22BP) was significantly decreased in Langerhans cells. Taken together, our study demonstrates that dupilumab effectively dampens conventional type 2 inflammation in DAHND lesions, with concomitant hyperactivation of IL22-associated responses.

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