Nataraja Champa, Dankers Wendy, Flynn Jacqueline, Lee Jacinta P W, Zhu Wendy, Vincent Fabien B, Gearing Linden J, Ooi Joshua, Pervin Mehnaz, Cristofaro Megan A, Sherlock Rochelle, Hasnat Md Abul, Harris James, Morand Eric F, Jones Sarah A
Monash University Centre for Inflammatory Disease, School of Clinical Sciences at Monash Health, Melbourne, VIC, Australia.
Centre for Innate Immunity and Infectious Diseases, Department of Molecular and Translational Science, Hudson Institute, Melbourne, VIC, Australia.
Front Immunol. 2021 Apr 6;12:652800. doi: 10.3389/fimmu.2021.652800. eCollection 2021.
Glucocorticoid-induced leucine zipper (GILZ) mimics many of the anti-inflammatory effects of glucocorticoids, suggesting it as a point of therapeutic intervention that could bypass GC adverse effects. We previously reported that GILZ down-regulation is a feature of human SLE, and loss of GILZ permits the development of autoantibodies and lupus-like autoimmunity in mice. To further query the contribution of GILZ to protection against autoimmune inflammation, we studied the development of the lupus phenotype in Lyn-deficient (Lyn) mice in which GILZ expression was genetically ablated. In Lyn mice, splenomegaly, glomerulonephritis, anti-dsDNA antibody titres and cytokine expression were exacerbated by GILZ deficiency, while other autoantibody titres and glomerular immune complex deposition were unaffected. Likewise, in patients with SLE, was inversely correlated with , and in SLE patients not taking glucocorticoids, was also inversely correlated with and . This suggests that at the onset of autoimmunity, GILZ protects against tissue injury by modulating pro-inflammatory pathways, downstream of antibodies, to regulate the cycle of inflammation in SLE.
糖皮质激素诱导亮氨酸拉链蛋白（GILZ）模拟了糖皮质激素的许多抗炎作用，这表明它可作为一种治疗干预靶点，从而规避糖皮质激素的不良反应。我们之前报道过，GILZ下调是人类系统性红斑狼疮（SLE）的一个特征，并且GILZ缺失会使小鼠产生自身抗体并出现狼疮样自身免疫。为了进一步探究GILZ在抵御自身免疫性炎症中的作用，我们研究了GILZ基因敲除的 Lyn缺陷（Lyn-/-）小鼠中狼疮表型的发展情况。在Lyn-/-小鼠中，GILZ缺陷会加剧脾肿大、肾小球肾炎、抗双链DNA抗体滴度及细胞因子表达，而其他自身抗体滴度及肾小球免疫复合物沉积则未受影响。同样，在SLE患者中，（此处原文缺失具体指标，无法准确翻译）与（此处原文缺失具体指标，无法准确翻译）呈负相关，并且在未服用糖皮质激素的SLE患者中，（此处原文缺失具体指标，无法准确翻译）也与（此处原文缺失具体指标，无法准确翻译）及（此处原文缺失具体指标
