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

Author

Listed:
  • 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
    New York Medical College)

  • 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)

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.

Suggested Citation

  • Christine Bangert & Natalia Alkon & Sumanth Chennareddy & Tamara Arnoldner & Jasmine P. Levine & Magdalena Pilz & Marco A. Medjimorec & John Ruggiero & Emry R. Cohenour & Constanze Jonak & William Dam, 2024. "Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46540-0
    DOI: 10.1038/s41467-024-46540-0
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    References listed on IDEAS

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    1. Keisha Findley & Julia Oh & Joy Yang & Sean Conlan & Clayton Deming & Jennifer A. Meyer & Deborah Schoenfeld & Effie Nomicos & Morgan Park & Heidi H. Kong & Julia A. Segre, 2013. "Topographic diversity of fungal and bacterial communities in human skin," Nature, Nature, vol. 498(7454), pages 367-370, June.
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    3. Cheng-Cheng Deng & Yong-Fei Hu & Ding-Heng Zhu & Qing Cheng & Jing-Jing Gu & Qing-Lan Feng & Li-Xue Zhang & Ying-Ping Xu & Dong Wang & Zhili Rong & Bin Yang, 2021. "Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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