Dataset related to article "Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome"

This record contains data related to article "Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome" Abstract <strong>Background: </strong> Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS). <strong>Objective: </strong> The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified. <strong>Methods: </strong> We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2^R229Q/R229Q (Rag2^R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt. <strong>Results: </strong> We show that memory/activated T cells from patients with OS and from the Rag2^R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad T_h1/T_h2/T_h17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2^R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2^R229Q mice results in increased frequency of Ccr4⁺ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by T_h1 effector T cells. <strong>Conclusions: </strong> These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS.本数据集收录与论文《Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome》（《Omenn综合征中皮肤屏障渗漏与肠道炎症驱动皮肤疾病》）相关的数据，并附该论文摘要。<strong>背景：</strong> 早发性重症红皮病伴肠道炎症、组织内大量寡克隆活化T细胞浸润，是Omenn综合征（OS）的标志性特征。<strong>目的：</strong> 肠道稳态紊乱对OS皮肤表现的影响仍有待阐明。<strong>方法：</strong> 本研究分析了15例OS患者队列，以及129Sv/C57BL/6背景的Rag2^R229Q/R229Q（Rag2^R229Q）敲入小鼠模型。通过流式细胞术（flow cytometry）分析循环淋巴细胞的归巢表型；采用酶联免疫吸附试验（ELISA）检测血清中的炎症细胞因子与趋化因子，通过免疫组织化学（immunohistochemistry）与原位RNA杂交（in situ RNA hybridization）分析皮肤活检样本中的相关指标；通过葡聚糖硫酸钠（dextran sulfate sodium salt）诱导小鼠实验性结肠炎。<strong>结果：</strong> 本研究证实，OS患者及Rag2^R229Q OS小鼠模型的记忆/活化T细胞可高表达皮肤归巢受体皮肤淋巴细胞相关抗原（cutaneous lymphocyte associated antigen）与CC趋化因子受体4（CCR4，Ccr4），同时伴随C-C基序配体17、22（C-C motif ligands 17、22）水平升高；血清脂多糖（LPS）水平亦有所升高。在外周血与皮肤组织中均可检测到广泛的Th1/Th2/Th17炎症特征。Rag2^R229Q小鼠皮肤中Toll样受体4（Tlr4）表达升高，且与局部或全身给予LPS后皮肤炎症加剧相关。同样地，在Rag2^R229Q小鼠中加重结肠炎可使脾脏Ccr4⁺ T细胞频率升高，并加剧皮肤炎症，具体表现为表皮增厚、上皮细胞活化增强以及Th1效应T细胞真皮浸润增加。<strong>结论：</strong> 上述结果证实，肠道与皮肤间存在相互作用，可维持OS患者的皮肤炎症状态。