Section of Rheumatology, Department of Medicine, Temple University, Philadelphia, PA 19140, USA.
Division of Immunology, Allergy and Rheumatology, Department of Internal Medicine, College of Medicine, University of Cincinnati, OH 45267, USA.
Dis Markers. 2019 Jul 9;2019:7838195. doi: 10.1155/2019/7838195. eCollection 2019.
Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease associated with impaired immune system regulation. The exact mechanisms of SLE development remain to be elucidated. TAM receptor tyrosine kinases (RTKs) are important for apoptotic cell clearance, immune homeostasis, and resolution of immune responses. TAM deficiency leads to lupus-like autoimmune diseases. Activation of TAM receptors leads to proteolytic cleavage of the receptors, generating soluble forms of TAM. Circulating TAM receptors have an immunoregulatory function and may also serve as biomarkers for disease prognosis. Here, we review the biological function and signaling of TAM RTKs in the development and pathogenesis of lupus and lupus nephritis. Targeting Gas6/TAM pathways may be of therapeutic benefit. A discussion of potential TAM activation and inhibition in the treatment of lupus and lupus nephritis is included.
系统性红斑狼疮（SLE）是一种多器官自身免疫性疾病，与免疫系统调节受损有关。SLE 的发展的确切机制仍有待阐明。TAM 受体酪氨酸激酶（RTKs）对于清除凋亡细胞、免疫稳态和免疫反应的解决非常重要。TAM 缺乏会导致狼疮样自身免疫性疾病。TAM 受体的激活导致受体的蛋白水解切割，产生 TAM 的可溶性形式。循环 TAM 受体具有免疫调节功能，也可以作为疾病预后的生物标志物。在这里，我们综述了 TAM RTKs 在狼疮和狼疮性肾炎的发生和发病机制中的生物学功能和信号转导。靶向 Gas6/TAM 途径可能具有治疗益处。讨论了在治疗狼疮和狼疮性肾炎中 TAM 的潜在激活和抑制。
