Abstract：
Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.
摘要：
在淋巴器官中建立的免疫调节机制对于预防自身免疫至关重要。然而,在非淋巴组织中是否存在类似机制尚不清楚.通过转录组学和脂质组学分析，我们发现银屑病和脂肪酸代谢之间存在负相关性，还有Th2签名。肝脏X受体（LXR）和过氧化物酶体增殖物激活受体γ（PPARγ）的稳态表达对于维持脂肪酸代谢和赋予小鼠对牛皮癣的抵抗力至关重要。信号转导和转录激活因子6（STAT6）的扰动降低了LXR和PPARγ的稳态水平。此外，缺乏STAT6，白细胞介素4受体α（IL-4Rα）的小鼠，或IL-13，而不是IL-4，表现出对牛皮癣的易感性增加。在稳定状态下,先天淋巴细胞（ILC）是IL-13的主要生产者。在人类皮肤中，抑制补品2型免疫会加剧牛皮癣样炎症和IL-17A，而激活LXR或PPARγ抑制它们。因此，我们认为补品2型免疫，由产生IL-13的ILC驱动，代表抑制自身免疫并维持皮肤脂质稳态的关键组织检查点。
