The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, The University of Copenhagen, Copenhagen, Denmark.
Respiratory Research Unit, Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark.
Contact Dermatitis. 2023 Nov;89(5):323-334. doi: 10.1111/cod.14409. Epub 2023 Aug 24.
The junctional adhesion molecule-like protein (JAML) plays important roles in wound healing and activation of epidermal γδ T cells in mice. Whether JAML plays a role in contact hypersensitivity (CHS), the animal model of allergic contact dermatitis (ACD), is not known.
To examine the role of JAML in CHS, we used various mouse models of CHS in JAML knockout (KO) and wild-type (WT) mice. Furthermore, the expression of the JAML ligand coxsackievirus and adenovirus receptor (CXADR) on keratinocytes was accessed in vitro and in vivo.
JAML KO mice had a diminished inflammatory response during both the sensitization and elicitation phase of CHS and had reduced numbers of CD8 and CD4 T cells in the epidermis. Furthermore, interferon γ (IFNγ), interleukin 1β (IL-1β) and CXCL10 production were significantly reduced in JAML KO mice during the elicitation phase. We found that CD8 T cells express JAML and that JAML is essential for rapid flare-up responses to contact allergens. Finally, we show that keratinocytes up-regulate the JAML ligand CXADR following exposure to contact allergens.
Our study is the first to show a central role of JAML in CHS and reveals a potential new target for the treatment of ACD in humans.
连接黏附分子样蛋白（JAML）在小鼠的伤口愈合和表皮 γδ T 细胞的激活中发挥重要作用。JAML 是否在接触性超敏反应（CHS），即变应性接触性皮炎（ACD）的动物模型中发挥作用尚不清楚。
为了研究 JAML 在 CHS 中的作用，我们在 JAML 敲除（KO）和野生型（WT）小鼠中使用了各种 CHS 小鼠模型。此外，我们还在体外和体内研究了角质形成细胞上 JAML 配体柯萨奇病毒和腺病毒受体（CXADR）的表达情况。
JAML KO 小鼠在 CHS 的致敏和激发阶段的炎症反应减弱，表皮中的 CD8 和 CD4 T 细胞数量减少。此外，在激发阶段，JAML KO 小鼠的干扰素 γ（IFNγ）、白细胞介素 1β（IL-1β）和 CXCL10 产生显著减少。我们发现 CD8 T 细胞表达 JAML，并且 JAML 对于对接触变应原的快速爆发反应是必需的。最后，我们表明角质形成细胞在接触变应原后上调 JAML 配体 CXADR。
本研究首次表明 JAML 在 CHS 中具有核心作用，并揭示了人类 ACD 治疗的一个新的潜在靶点。
