狼疮性肾炎（LN）是系统性红斑狼疮（SLE）最常见的器官受累之一，LN患者肾脏中存在多种致病性免疫细胞浸润和激活、调节性T细胞受损及多种自身抗体和致炎因子的积累。因此，修复肾脏组织免疫失衡、抑制自身免疫反应是LN临床治疗的迫切需求。我们在国内外首次证明，与传统治疗相比，低剂量IL-2可更高效地改善LN疗效，但其作用机制还不清楚。基于前期研究，我们提出以下科学假说：低剂量IL-2选择性诱导表达皮肤淋巴细胞抗原（CLA）的Treg亚群，该Treg亚群可能倾向于向肾炎组织趋化迁移并抑制LN致病性免疫细胞，从而改善LN肾脏组织免疫平衡、使LN改善的效率更高。为验证该假说，本课题将首次对低剂量IL-2治疗LN过程中CLA+Treg细胞亚群的表型、功能、趋化运动特点及其分化调控机制进行研究，有望深入认识低剂量IL-2改善LN疗效的作用机制，为改善LN治疗提供新的靶点和实验依据。

Lupus nephritis (LN) is one of the most common organ involvement in systemic lupus erythematosus (SLE). In the kidneys of patients with LN, infiltration of a variety of pathogenic immune cell subsets, impairment of regulatory T cells (Tregs) and accumulation of multiple autoantibodies and inflammatory cytokines are detected. So there is an urgent need of restoring the immune balance and suppress autoimmune response in the kidney of LN to improve LN treatment. Our previous studies first showed that low-dose IL-2 therapy efficiently treated SLE and improved LN more preferentially than other organ involvement. However, the mechanism of low-dose IL-2’s preferential efficacy on LN is still elusive. Based on our preliminary study, we propose that low-dose IL-2 treatment may specifically induce the expansion of CLA+ Treg cell subset which may be prone to migrate to the inflammation sites in LN kidney and play the immunoregulatory role on the LN associated pathogenic immune cell populations. This process may help restore the immune homeostasis in LN kidney and improve LN treatment more efficiently. To confirm this hypothesis, in this project, we will identify the phenotypes, immunoregulatory functions, characteristics of chemotaxis, regulatory pathways of CLA+ Tregs in LN condition and IL-2 treatment. This project will further uncover the mechanism of low-dose IL-2 therapy on LN and provide novel treatment targets, experimental evidence and ideas to improve future LN treatment.