Matos Tiago R, O'Malley John T, Lowry Elizabeth L, Hamm David, Kirsch Ilan R, Robins Harlan S, Kupper Thomas S, Krueger James G, Clark Rachael A
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
J Clin Invest. 2017 Nov 1;127(11):4031-4041. doi: 10.1172/JCI93396. Epub 2017 Sep 25.
In psoriasis, an IL-17-mediated inflammatory skin disease, skin lesions resolve with therapy, but often recur in the same locations when therapy is discontinued. We propose that residual T cell populations in resolved psoriatic lesions represent the pathogenic T cells of origin in this disease. Utilizing high-throughput screening (HTS) of the T cell receptor (TCR) and immunostaining, we found that clinically resolved psoriatic lesions contained oligoclonal populations of T cells that produced IL-17A in both resolved and active psoriatic lesions. Putative pathogenic clones preferentially utilized particular Vβ and Vα subfamilies. We identified 15 TCRβ and 4 TCRα antigen receptor sequences shared between psoriasis patients and not observed in healthy controls or other inflammatory skin conditions. To address the relative roles of αβ versus γδ T cells in psoriasis, we carried out TCR/δ HTS. These studies demonstrated that the majority of T cells in psoriasis and healthy skin are αβ T cells. γδ T cells made up 1% of T cells in active psoriasis, less than 1% in resolved psoriatic lesions, and less than 2% in healthy skin. All of the 70 most frequent putative pathogenic T cell clones were αβ T cells. In summary, IL-17-producing αβ T cell clones with psoriasis-specific antigen receptors exist in clinically resolved psoriatic skin lesions. These cells likely represent the disease-initiating pathogenic T cells in psoriasis, suggesting that lasting control of this disease will require suppression of these resident T cell populations.
在银屑病（一种由白细胞介素 - 17介导的炎症性皮肤病）中，皮肤病变经治疗后会消退，但在停止治疗后通常会在相同部位复发。我们提出，消退的银屑病病变中的残余T细胞群体代表了该疾病的致病性起始T细胞。通过对T细胞受体（TCR）进行高通量筛选（HTS）和免疫染色，我们发现临床消退的银屑病病变含有T细胞的寡克隆群体，这些T细胞在消退和活动期的银屑病病变中均产生白细胞介素 - 17A。推定的致病克隆优先利用特定的Vβ和Vα亚家族。我们鉴定出银屑病患者之间共有的15个TCRβ和4个TCRα抗原受体序列，在健康对照或其他炎症性皮肤病中未观察到。为了探讨αβ与γδ T细胞在银屑病中的相对作用，我们进行了TCR/δ HTS。这些研究表明，银屑病和健康皮肤中的大多数T细胞是αβ T细胞。γδ T细胞在活动期银屑病中占T细胞的1%，在消退的银屑病病变中不到1%，在健康皮肤中不到2 %。70个最常见的推定致病T细胞克隆均为αβ T细胞。总之，在临床消退的银屑病皮肤病变中存在具有银屑病特异性抗原受体的产生白细胞介素 - 17的αβ T细胞克隆。这些细胞可能代表了银屑病中引发疾病的致病性T细胞，这表明对该疾病的持久控制将需要抑制这些驻留T细胞群体。
