Phenotypic and functional alterations of pDCs in lupus-prone mice.

Zhenyuan Zhou,Rong Qiu,Li Wu,Xinfang Huang,Yan Wang,Xiao Han,Jianyang Ma,Yingying Zhou,Chunyuan Xiao,Nan Shen

doi:10.1038/srep20373

Abstract

Plasmacytoid dendritic cells (pDCs) were considered to be the major IFNα source in systemic lupus erythematosus (SLE) but their phenotype and function in different disease status have not been well studied. To study the function and phenotype of pDCs in lupus-prone mice we used 7 strains of lupus-prone mice including NZB/W F1, NZB, NZW, NZM2410, B6.NZMSle1/2/3, MRL/lpr and BXSB/Mp mice and C57BL/6 as control mice. Increased spleen pDC numbers were found in most lupus mice compared to C57BL/6 mice. The IFNα-producing ability of BM pDCs was similar between lupus and C57BL/6 mice, whereas pDCs from the spleens of NZB/W F1 and NZB mice produced more IFNα than pDCs from the spleens of C57BL/6 mice. Furthermore, spleen pDCs from MRL-lpr and NZM2410 mice showed increased responses to Tlr7 and Tlr9, respectively. As the disease progressed, IFN signature were evaluated in both BM and spleen pDC from lupus prone mice and the number of BM pDCs and their ability to produce IFNα gradually decreased in lupus-prone mice. In conclusion, pDC are activated alone with disease development and its phenotype and function differ among lupus-prone strains, and these differences may contribute to the development of lupus in these mice.

Highlights

System lupus erythematosus (SLE) is the most common autoimmune disease in young women
The numbers of BM plasmacytoid dendritic cells (pDCs) in New Zealand White (NZW), NZM2410 and B6.NZMSle1/2/3 mice and male BXSB/Mp mice compared to that in C57BL/6 mice were not significantly different. Both the lymph nodes (LNs) and thymus glands contained fewer pDCs, suggesting that the LNs and thymus may contribute relatively little to the high IFN expression (Fig. 1C,D)
CD4+ T cells contribute to the disease of New Zealand Black (NZB) mice because of the types of MHC-II molecules expressed by these mice

Summary

Introduction

System lupus erythematosus (SLE) is the most common autoimmune disease in young women. Recent studies have found that neutralizing IFNα can decrease the autoantibody titer and relieve clinical symptoms in both human SLE patients and lupus-prone mice[3,4,5,6]. New Zealand Black (NZB) × New Zealand White (NZW) F1 (NZB/W F1) mice represent the first strain developed to exhibit symptoms that mimic lupus, including high titers of autoantibodies and severe nephritis[9]. This strain has been widely used in studies of lupus pathogenesis. We hypothesize that pDCs may represent an important IFNα source in both SLE patients and lupus-prone mice. In the advanced lupus stage, the number and function of pDCs changed according to the development of the disease

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Conclusion