Autor: |
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, Patrick M. Brunner |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-024-46540-0 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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