肾脏与免疫系统关系密切，其中肾小球足细胞不仅具有调节肾小球滤过率、参与肾小球基底膜重构等功能，而且还是肾脏发挥固有免疫功能，促进炎症并驱动和调节适应性免疫应答的关键细胞之一。足细胞抗原的确定为足细胞参与肾小球疾病中的免疫机制提供直接的证据。除足细胞表达MHC I类及II类分子、共刺激因子及粘附因子和其具有抗原递呈能力及T细胞激活功能外，对于足细胞如何参与固有免疫的调控尚不明确。模式识别受体（PRR）是细胞固有免疫的重要调控因子，但其又如何调控足细胞的固有免疫并不清楚。本课题拟利用生物芯片及Cre-LoxP足细胞特异性PRR基因敲除小鼠等手段主要探讨（一）明确足细胞中PRR参与肾脏区域免疫及肾小球疾病中的亚型及作用；（二）足细胞PRR的表观遗传学调控机制; （三）在肾小球疾病中足细胞PRR与补体系统的相互调控及作用。本课题将拓展对足细胞免疫功能的认识，为肾小球疾病的防治提供新靶点和思路。

Kidney is a vital organ which is associated with systemic immune and autoimmune diseases and the contribution of local immune activity of the kidney to the development of glomerular diseases because of the glomerular cells’ unique structure and functions. Among glomerular cells, podocytes are highly specialized, terminally differentiated epithelial cells that are integral components of the renal glomerular filtration barrier, which are vulnerable to a variety of injuries and as a result, they undergo a series of changes ranging from hypertrophy, detachment, autophagy to apoptosis. As podocytes have limited ability to repair and regenerate, the extent of podocyte injury is considered as a major prognostic determinant in end-stage renal disease (2). Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are the two major forms of acquired glomerular disease that are widely accepted to be podocytopathies. In addition, there is mounting evidence of podocyte injury in a variety of other renal diseases such as diabetic nephropathy (DN), membranous glomerulonephritis (MGN) and IgA nephropathy. In these conditions, podocytes lose specific markers of differentiation, undergo foot process effacement and eventual detachment, and reduce the capacity to maintain the glomerular filtration barrier, thereby resulting in proteinuria. In addition, podocytes have immune potential and function as “part-time” immune cells that are involved in the glomerular disease development by the fact that the expression of immune-associated receptors, phagocytosis and antigen presentation activity of podocytes and stimulating T cells and neutrophils by podocytes. However, it still keep unclear the innate immune system and the regulatory mechanisms in podocytes. The innate immune system includes several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and C-type lectin receptors (CLR). These receptors detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the extracellular and intracellular space. Intracellular NLRs constitute inflammasomes, which activate and release caspase-1, IL-1β, and IL-18 thereby initiating an inflammatory response. Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the development and progression of podocyte injuries. The present study is to determine how PRR-mediated innate immune system-driven inflammatory processes in podocytes can lead to glomerular disease by in vitro and in vivo animal studies by Cre-LOXP mice. Our study may provide novel insights into the immune mechanism underlying glomerular disease development. Pharmacological targeting of PRR-mediated immune signaling pathways at multiple levels may provide a novel approach for treatment of glomerular disease.