The Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
The Division of Pediatric Nephrology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Clin Immunol. 2014 Sep;154(1):49-65. doi: 10.1016/j.clim.2014.06.007. Epub 2014 Jun 24.
The onset of autoantibodies in systemic autoimmunity can be the result of a breakdown in tolerance at multiple checkpoints. Genetic, hormonal, and immunological factors can combine with environmental influences to accelerate the onset of disease and aggravate disease outcome. Here, we describe a novel mechanism relating to the regulatory role of Neutrophil Gelatinase Associated Lipocalin (NGAL) in modulating the levels of autoantibodies in pristane induced lupus. Following a single injection of pristane intraperitoneally, NGAL expression was induced in both the serum and spleen. Furthermore, NGAL deficient mice were more susceptible to the induction of pristane stimulated autoimmunity, and displayed higher numbers of autoantibody secreting cells and increased expression of activation induced cytidine deaminase (AID) and other inflammatory mediators in the spleen. In contrast, kidney damage was milder in NGAL deficient mice, indicating that NGAL was detrimental in autoantibody mediated kidney disease. These studies indicate that NGAL plays differential roles in different tissues in the context of lupus, and suggest a previously unrecognized role for NGAL in adaptive immunity.
自身免疫性疾病中自身抗体的出现可能是多个检查点的耐受机制崩溃的结果。遗传、激素和免疫因素与环境影响相结合，可以加速疾病的发生，并加重疾病的结局。在这里，我们描述了一种新的机制，涉及中性粒细胞明胶酶相关脂质运载蛋白（NGAL）在调节 pristane 诱导狼疮中自身抗体水平方面的调节作用。在腹腔内单次注射 pristane 后，血清和脾脏中均诱导表达了 NGAL。此外，NGAL 缺陷型小鼠对 pristane 刺激的自身免疫的诱导更为敏感，并且在脾脏中显示出更多的自身抗体分泌细胞和激活诱导的胞苷脱氨酶（AID）和其他炎症介质的表达增加。相比之下，NGAL 缺陷型小鼠的肾脏损伤较轻，表明 NGAL 在自身抗体介导的肾脏疾病中是有害的。这些研究表明，NGAL 在狼疮的不同组织中发挥不同的作用，并提示 NGAL 在适应性免疫中具有以前未被认识的作用。
