Lupus nephritis is one of most severe complications of systemic erythematosus lupus and current approaches are not curative for lupus nephritis. Although CD4+Foxp3+ regulatory T cells (Treg) are crucial for prevention of autoimmunity, the therapeutic effect of these cells on lupus nephritis is not satisfactory. We previously reported that CD8+CD103+ Treg induced ex vivo with TGF-β1 and IL-2 (CD8+CD103+ iTreg), regardless of Foxp3 expression, displayed potent immunosuppressive effect on Th cell response and had therapeutic effect on Th cell-mediated colitis. Here, we tested whether CD8+CD103+ iTreg can ameliorate lupus nephritis and determined potential molecular mechanisms. Adoptive transfer of CD8+CD103+ iTreg but not control cells to chronic graft-versus-host disease with a typical lupus syndrome showed decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, lowered renal deposition of IgG/C3, and improved survival. CD8+CD103+ iTreg cells suppressed not only T helper cells but also B cell responses directly that may involve in both TGF-β and IL-10 signals. Using RNA-seq, we demonstrated CD8+CD103+ iTreg have its own unique expression profiles of transcription factors. Thus, current study has identified and extended the target cells of CD8+CD103+ iTreg and provided a possible application of this new iTreg subset on lupus nephritis and other autoimmune diseases.
Background: Despite the considerable efforts made to address the issue of brucellosis worldwide, its prevalence in dairy products continues to be difficult to estimate and represents a key public health issue around the world today. The aim of the present study was to better understand the epidemiology of this disease in mainland China. We set out to investigate the yearly spatial distribution and possible hotspots of the disease. Methods: Human brucellosis data from mainland China between 2007 and 2016 were collected from the China Information System for Disease Control and Prevention. A geographic information system ArcGIS10.3 (ESRI, Redlands) was used to identify potential changes in the spatial and temporal distribution of human brucellosis in mainland China during the study period. These distributions were evaluated using three-dimensional trend analysis and spatial autocorrelation analyse. A gravity-center was used to analyse the migration track of human brucellosis. Results: A total of 399,578 cases of human brucellosis were reported during the 10-year study period. The monthly incidence of brucellosis in China demonstrates clear seasonality. Spring and summer are the peak seasons, while May is the peak month for brucellosis. Three-dimensional trend analysis suggests that brucellosis is on the rise from south to north, and that the epidemic situation in northern China is more severe. Between 2007 and 2016, the overall migration distance of the brucellosis incidence gravity-center was 906.43 km, and the direction was southwest. However, the overall gravity center of brucellosis was still in the northern part of China. In the global autocorrelation analysis, brucellosis in China demonstrated a non-random distribution between 2013 and 2014, with spatial autocorrelation (Z > 1.96, P < 0.05) and a clustering trend, while no clustering trend was found from 2007 to 2012 or from 2015 to 2016. In the local autocorrelation analysis, a Low-Low cluster phenomenon was found in the south of China in 2013 and 2014. Conclusion: Human brucellosis remains a widespread challenge, particularly in northern China. The hotspots highlight potential high-risk areas which may require special plans and resources for monitoring and controlling the disease.
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