The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, The University of Copenhagen, Copenhagen, Denmark.
Department of Dermatology and Allergy, National Allergy Research Center, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
Contact Dermatitis. 2023 Dec;89(6):442-452. doi: 10.1111/cod.14414. Epub 2023 Sep 12.
Allergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal-resident memory CD8 T (T ) cells play a key role. The mechanisms involved in the activation of CD8 T cells during allergic flare-up responses are not understood.
The expression of CD100 and its ligand Plexin B2 on CD8 T cells and keratinocytes before and after allergen exposure was determined by flow cytometry and RT-qPCR. The role of CD100 in the inflammatory response during the challenge phase of ACD was determined in a model of ACD in CD100 knockout and wild-type mice.
We show that CD8 T cells express CD100 during homeostatic conditions and up-regulate it following re-exposure of allergen-experienced skin to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB). Furthermore, Plexin B2 is up-regulated on keratinocytes following exposure to some contact allergens. We show that loss of CD100 results in a reduced inflammatory response to DNFB with impaired production of IFNγ, IL-17A, CXCL1, CXCL2, CXCL5, and IL-1β and decreased recruitment of neutrophils to the epidermis.
Our study demonstrates that CD100 is expressed on CD8 T cells and is required for full activation of CD8 T cells and the flare-up response of ACD.
变应性接触性皮炎（ACD）是一种具有复杂病理生理学的炎症性疾病，其中表皮驻留记忆 CD8 T（T）细胞起着关键作用。在过敏发作反应中，CD8 T 细胞被激活的机制尚不清楚。
通过流式细胞术和 RT-qPCR 确定 CD8 T 细胞和角质形成细胞在过敏原暴露前后 CD100 及其配体 Plexin B2 的表达。在 CD100 敲除和野生型小鼠 ACD 模型中，确定了 CD100 在 ACD 挑战阶段炎症反应中的作用。
我们表明，CD8 T 细胞在稳态条件下表达 CD100，并在再次暴露于实验性接触过敏原 1-氟-2,4-二硝基苯（DNFB）的过敏原暴露的皮肤后上调其表达。此外，某些接触过敏原暴露后，角质形成细胞上调 Plexin B2。我们表明，CD100 的缺失导致对 DNFB 的炎症反应减弱，IFNγ、IL-17A、CXCL1、CXCL2、CXCL5 和 IL-1β 的产生减少，表皮中性粒细胞募集减少。
我们的研究表明，CD100 表达在 CD8 T 细胞上，是 CD8 T 细胞充分激活和 ACD 发作反应所必需的。
