Evers Beatrix D G, Hils Miriam, Heuser Christoph, Hölge Inga M, Argiriu Désirée, Skabytska Yuliya, Kaesler Susanne, Posch Christian, Knolle Percy A, Biedermann Tilo
Department of Dermatology and Allergology, TUM School of Medicine, Technical University of Munich (TUM), Munich, Germany.
Leibniz Institute for Immunotherapy, Department of Functional Immune Cell Modulation, Regensburg, Germany.
JID Innov. 2023 Apr 25;3(4):100204. doi: 10.1016/j.xjidi.2023.100204. eCollection 2023 Jul.
Innate lymphoid cells (ILCs) are gatekeepers in barrier organs, where they maintain tissue integrity and contribute to host defense as well as tissue repair. Inappropriate activation of ILCs, however, can lead to immunopathology with detrimental results. In this study, we focused on type 1 ILCs (ILC1s), which under inflammatory conditions constitute a poorly defined population with ambiguous functions. To delineate the properties of ILC1s in skin pathology, we used the well-established mouse model of imiquimod-induced psoriasis. Although ILC1s represented a minority among cutaneous lymphocytes in vehicle-treated controls, they rapidly expanded during early psoriasis and ultimately increased by >20-fold. This rapid increase was verified using two additional psoriasis models. Inflammatory ILC1s from imiquimod-treated skin were defined as CD44, CXCR6, and CD11b and substantially contributed to TNF-α and GM-CSF production, rendering them a potential candidate to shape the inflammatory infiltrate. In accordance with the psoriasis-specific microenvironment, skin ILC1s upregulated the IL-23 receptor whereas expression of the IL-12Rβ2 subunit was diminished. As a consequence, neutralization of IL-12 only had a minor impact, whereas blocking IL-23 reduced both ILC1 abundance and disease severity. Together, our findings identify skin ILC1s as a likely player in early psoriasis and a prospective target for therapeutic approaches.
固有淋巴细胞（ILCs）是屏障器官中的守门人，它们维持组织完整性，有助于宿主防御以及组织修复。然而，ILCs的不适当激活会导致免疫病理学，产生有害结果。在本研究中，我们聚焦于1型固有淋巴细胞（ILC1s），在炎症条件下，它们构成了一群功能不明确、作用模糊的细胞群体。为了阐明皮肤病理学中ILC1s的特性，我们使用了已建立的咪喹莫特诱导的银屑病小鼠模型。虽然在使用赋形剂处理的对照组中，ILC1s在皮肤淋巴细胞中占少数，但在银屑病早期它们迅速扩增，最终增加了20倍以上。使用另外两种银屑病模型验证了这种快速增加。来自咪喹莫特处理皮肤的炎性ILC1s被定义为CD44、CXCR6和CD11b，并且对TNF-α和GM-CSF的产生有显著贡献，使其成为塑造炎性浸润细胞的潜在候选细胞群体。与银屑病特异性微环境一致，皮肤ILC1s上调IL-23受体，而IL-12Rβ2亚基的表达减少。因此，中和IL-12只有轻微影响，而阻断IL-23则可降低ILC1的丰度和疾病严重程度。总之，我们的研究结果表明皮肤ILC1s可能是早期银屑病的参与者以及治疗方法的潜在靶点。
