Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
Front Immunol. 2022 Jun 15;13:874778. doi: 10.3389/fimmu.2022.874778. eCollection 2022.
Alopecia areata (AA) is an autoimmune disease mediated by NKG2D-expressing cytotoxic T lymphocytes destroying hair follicles in the skin. It is one of the most common autoimmune diseases, but there is no effective treatment modality approved by the FDA. Regulatory T cells (Tregs) are crucial for suppressing autoreactive T cells, and in the skin, they promote hair growth by inducing anagen. Based on this, we tested the therapeutic potential of expanded Tregs in AA using the C3H/HeJ mouse model. In mice with AA, NKG2D-expressing CD8 T cells widely infiltrate both haired and hairless skin areas, which have tissue-resident memory T-cell phenotypes. Tregs in the skin express CD25, CTLA-4, GATA-3, and Jagged1 and efficiently proliferate with IL-2 cytokine antibody complex. However, expanding Tregs in the skin did not induce anagen in normal mice, indicating that they are necessary but not sufficient for anagen induction. Also, they fail to suppress autoreactive CD8 T cells in the skin to reverse established AA in C3H/HeJ mice. These results suggest that Treg expansion alone is not sufficient for AA treatment, and combined immunotherapy is required.
斑秃（AA）是一种由 NKG2D 表达的细胞毒性 T 淋巴细胞介导的自身免疫性疾病，可破坏皮肤中的毛囊。它是最常见的自身免疫性疾病之一，但美国食品和药物管理局（FDA）尚未批准有效的治疗方法。调节性 T 细胞（Tregs）对于抑制自身反应性 T 细胞至关重要，在皮肤中，它们通过诱导生长期来促进头发生长。基于此，我们使用 C3H/HeJ 小鼠模型测试了 Tregs 扩增在 AA 中的治疗潜力。在 AA 小鼠中，NKG2D 表达的 CD8 T 细胞广泛浸润有毛和无毛皮肤区域，具有组织驻留记忆 T 细胞表型。皮肤中的 Tregs 表达 CD25、CTLA-4、GATA-3 和 Jagged1，并可有效增殖。然而，在正常小鼠中，Tregs 的扩增并未诱导生长期，表明其对于生长期诱导是必要的，但不是充分的。此外，它们未能抑制皮肤中的自身反应性 CD8 T 细胞，从而无法逆转 C3H/HeJ 小鼠中已建立的 AA。这些结果表明，Treg 扩增本身不足以治疗 AA，需要联合免疫疗法。
