Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells

Christine Bangert, Natalia Alkon, Sumanth Chennareddy, Tamara Arnoldner, Jasmine P. Levine, Magdalena Pilz, Marco A. Medjimorec, John Ruggiero, Emry R. Cohenour, Constanze Jonak, William Damsky, Johannes Griss and Patrick M. Brunner ()
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Christine Bangert: Medical University of Vienna
Natalia Alkon: Medical University of Vienna
Sumanth Chennareddy: Icahn School of Medicine at Mount Sinai
Tamara Arnoldner: Medical University of Vienna
Jasmine P. Levine: Icahn School of Medicine at Mount Sinai
Magdalena Pilz: Medical University of Vienna
Marco A. Medjimorec: Medical University of Vienna
John Ruggiero: Icahn School of Medicine at Mount Sinai
Emry R. Cohenour: Icahn School of Medicine at Mount Sinai
Constanze Jonak: Medical University of Vienna
William Damsky: Yale School of Medicine
Johannes Griss: Medical University of Vienna
Patrick M. Brunner: Icahn School of Medicine at Mount Sinai

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown. We profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and compared data with untreated AD and healthy control skin. We show that dupilumab treatment was accompanied by normalization of IL-4/IL-13 downstream activity markers such as CCL13, CCL17, CCL18 and CCL26. By contrast, we found strong increases in type 22-associated markers (IL22, AHR) especially in oligoclonally expanded T cells, accompanied by enhanced keratinocyte activation and IL-22 receptor upregulation. Taken together, we demonstrate that dupilumab effectively dampens conventional type 2 inflammation in DAHND lesions, with concomitant hyperactivation of IL22-associated responses.

Date: 2024
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DOI: 10.1038/s41467-024-46540-0

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