银屑病 (PsO) 和银屑病关节炎 (PsA) 是影响皮肤和关节的免疫介导的炎症性疾病。大约 30% 的 PsO 患者随着时间的推移会发展为 PsA，这两种情况都与肿瘤坏死因子-α (TNF-α) 表达升高有关。 TNF-α 通过两种膜受体 TNFR1 和 TNFR2 介导其作用。虽然目前针对 TNFR1 和 TNFR2 受体的 TNF-α 中和剂构成了银屑病疾病的主要治疗方法，但由于机会性感染、结核病再激活和可能归因于 TNFR1 失活的恶性肿瘤的增加，其长期使用受到限制。最近的研究结果表明 TNFR2 在银屑病疾病中发挥着关键作用，其在整体 TNFR2 敲除 (TNFR2KO) 小鼠中的改善证明了这一点，但在 TNFR1KO 小鼠中却没有改善。 TNFR2KO 小鼠疾病表型的减少伴随着 DC 群体的减少。然而，TNFR2 在树突状细胞 (DC) 中的具体贡献仍不清楚。在这里，利用甘露寡糖 (MOS) 诱导的 PsA 模型，我们证明树突状细胞特异性 TNFR2 敲除小鼠 (DC-TNFR2KO) 的 PsA 样皮肤鳞屑和关节炎症显着减少。值得注意的是，对照小鼠 (TNFR2 fl/fl) 的 MOS 治疗导致脾脏中传统 1 型树突状细胞 (cDC1) 数量的增加，而 DC-TNFR2KO 小鼠的这种反应受到抑制。此外，与 MOS 刺激后的对照组相比，DC-TNFR2KO 小鼠的血清中白细胞介素 12 (IL-12)（一种 Th1 细胞激活剂）水平以及 Th1 细胞减少和干扰素 γ (IFN-γ) 水平降低。总之，我们的研究提供了令人信服的证据，支持 TNFR2 通过 cDC1/Th1 激活途径促进 PsA 样炎症的作用。

Psoriasis (PsO) and Psoriatic arthritis (PsA) are immune-mediated inflammatory diseases affecting the skin and joints. Approximately, 30% of patients with PsO develop PsA over time with both conditions being associated with elevated tumor necrosis factor-alpha (TNF-α) expression. TNF-α mediates its effect through two membrane receptors, TNFR1 and TNFR2. While current TNF-α-neutralizing agents, targeting both TNFR1 and TNFR2 receptors, constitute the primary treatment for psoriatic diseases, their long-term use is limited due to an increase in opportunistic infections, tuberculosis reactivation and malignancies likely attributed to TNFR1 inactivation. Recent findings suggest a pivotal role of TNFR2 in psoriatic disease, as evidenced by its amelioration in global TNFR2-knockout (TNFR2KO) mice, but not in TNFR1KO mice. The diminished disease phenotype in TNFR2KO mice is accompanied by a decrease in DC populations. However, the specific contribution of TNFR2 in dendritic cells (DCs) remains unclear. Here, utilizing a mannan-oligosaccharide (MOS)-induced PsA model, we demonstrate a significant reduction in PsA-like skin scaling and joint inflammation in dendritic cell-specific TNFR2 knockout mice (DC-TNFR2KO). Notably, MOS treatment in control mice (TNFR2 fl/fl) led to an increase in conventional type 1 dendritic cells (cDC1) population in the spleen, a response inhibited in DC-TNFR2KO mice. Furthermore, DC-TNFR2KO mice exhibited reduced levels of interleukin-12 (IL-12), a Th1 cell activator, as well as diminished Th1 cells, and interferon-gamma (IFN-γ) levels in the serum compared to controls following MOS stimulation. In summary, our study provides compelling evidence supporting the role of TNFR2 in promoting PsA-like inflammation through cDC1/Th1 activation pathways.