T cells and IL-17 in lupus nephritis

Abstract

Systemic lupus erythematosus (SLE) is a complicated autoimmune disorder characterized by autoantibodies production, immune complex formation, and immune dysregulation, resulting in damage of multiple organs including the kidney. Lupus nephritis (LN) is the most common severe manifestation of SLE involving the majority of patients. Even though there are a number of reports indicating that interleukin-17 (IL-17) and Th17 cells play important roles in the pathogenesis of LN, the precise molecular mechanisms underline the development of LN have not been totally elucidated. In this review, we briefly summarize general characteristics of T and IL-17 cells in SLE. In addition, we discuss in detail T cell signaling pathways which control IL-17 production in patients with LN and in glomerulonephritis in lupus-prone mice. A better understanding of signaling and gene regulation defects in LN will lead to the identification of novel therapeutic targets and predictive biomarkers for diagnosis and prognosis of this disease.

Keywords: Interleukin-17; Lupus nephritis; Systemic lupus erythematosus; T cells.

Figure 1

Lupus patients have an imbalance between Th17 and Treg cells. SLE: Systemic lupus erythematosus, TCR: T cell receptor, Th: T helper, Treg: regulatory T cell.

Figure 2

The aberrant T cell signaling in the pathogenesis of LN. SLE: Systemic lupus erythematosus, TCR: T cell receptor, PP2Ac: Protein phosphatase 2A catalytic subunit, CaMK4: Calcium/calmodulin-dependent protein kinase IV, ROCK: Rho-associated protein kinase, CREB: cAMP response element binding protein, IRF4: interferon regulatory factor 4, CREM: cAMP response element modulator, mTORC1: mammalian target of rapamycin complex 1, Th: T helper, Treg: regulatory T cell.