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度普利尤单抗相关的头颈部皮炎表现出由寡克隆扩增的 T 细胞介导的显著 22 型免疫特征。

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

机构信息

Department of Dermatology, Medical University of Vienna, Vienna, Austria.

Icahn School of Medicine at Mount Sinai, New York City, NY, USA.

出版信息

Nat Commun. 2024 Apr 2;15(1):2839. doi: 10.1038/s41467-024-46540-0.

DOI:10.1038/s41467-024-46540-0
PMID:38565563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10987549/
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.

摘要

度普利尤单抗（一种 IL4R 阻断抗体）已被证明对特应性皮炎（AD）的治疗具有临床疗效。除了结膜炎/睑缘炎外，新出现的头/颈部皮炎现在被认为是一种独特的副作用，在多达 10%的患者中发生。与 AD 不同的组织病理学特征提示存在药物作用，但确切的潜在机制尚不清楚。我们通过单细胞 RNA 测序对度普利尤单抗相关头颈部皮炎（DAHND）的活检样本进行了分析，并将数据与未经治疗的 AD 皮肤和健康对照皮肤进行了比较。结果显示，度普利尤单抗治疗可使 CCL13、CCL17、CCL18 和 CCL26 等 IL-4/IL-13 下游活性标志物的活性正常化。相比之下，我们发现 22 型相关标志物（IL22、AHR）显著增加，特别是在寡克隆扩增的 T 细胞中，同时伴有角质形成细胞的激活和 IL-22 受体的上调。总之，我们证明了度普利尤单抗可有效抑制 DAHND 病变中的传统 2 型炎症，同时伴有 IL22 相关反应的过度激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/dd7d3b8bfafb/41467_2024_46540_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/ee4cd4de455b/41467_2024_46540_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/f05e9fd110d3/41467_2024_46540_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/ac4045e48fbc/41467_2024_46540_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/2c76c955c894/41467_2024_46540_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/ae6f15479a7c/41467_2024_46540_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/4623f35e8014/41467_2024_46540_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/dd7d3b8bfafb/41467_2024_46540_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/8aa8c2d9bdb5/41467_2024_46540_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/1e40be3ceb85/41467_2024_46540_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/ee4cd4de455b/41467_2024_46540_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/f05e9fd110d3/41467_2024_46540_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/ac4045e48fbc/41467_2024_46540_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/2c76c955c894/41467_2024_46540_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/ae6f15479a7c/41467_2024_46540_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/4623f35e8014/41467_2024_46540_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20b3/10987549/dd7d3b8bfafb/41467_2024_46540_Fig9_HTML.jpg

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