Expression profiling of immune cells in systemic lupuserythematosus by single-cell RNA sequencing

Systemic lupus erythematosus(SLE)is a systemic autoimmune disease characterized by abnormal cellular and humoral immune responses and excessive autoantibody production.The precise pathologic mechanism of SLE remains elusive.The advent of single-cell RNA sequencing(scRNA-seq)enables unbiased analysis of the molecular differences of cell populations at the single-cell level.We used scRNA-seq to profile the transcriptomes of peripheral blood mononuclear cells from an SLE patient compared with a healthy control(HC).A total of 16,021 cells were analyzed and partitioned into 12 distinct clusters.The marker genes of each cluster and the four major immune cell types(B cells,CD4+T cells,CD8+T cells,myeloid cells,and NK cells)were determined.Moreover,several genes involved in antigen processing and presentation through MHCII were highly enriched.GO enrichment analyses revealed abnormal gene expression patterns and signaling pathways in SLE.Of note,pseudotime analysis revealed that there was a different lineage hierarchy in the peripheral blood mononuclear cells(PBMCs)of the SLE patient,indicating that the cell states were substantially altered under disease conditions.Our analysis provides a comprehensive map of the cell types and states of the PBMCs of SLE patients at the single-cell level for a better understanding of the pathogenesis,diagnosis,and treatment of SLE.

IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis

Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE.

Ecto-mesenchymal stem cells: a new player for immune regulation and cell therapy

Extensive studies have demonstrated that mesenchymal stem cells(MSCs)are multipotent mesoderm-derived stromal cells that can differentiate into a variety of cell types,including adipocytes,osteoblasts,chondrocytes,myocytes and neuronal cells.1 MSCs are found in numerous organs and tissues,including bone marrow,heart,lung,muscle,peripheral blood,adipose tissue,cartilage,synovium,dental pulp,tonsil,umbilical cord,placenta,thymus and olfactory mucosa.1 MSCs have been shown to possess potent immunosuppressive functions and tissue repair capacities,which have facilitated the clinical applications of MSCs in treating a diverse range of disorders involving angiogenesis and fibrosis,including rheumatic diseases and graft-versus-host diseases.2,3 Here,we provide a brief commentary on newly emerging evidence of the immunoregulatory function and potential application of ecto-mesenchymal stem cells.

A Symbol-Based Passband Doppler Tracking and Compensation Algorithm for Underwater Acoustic DSSS Communications

In this paper,we consider the problem of Doppler tracking and compensation for a direct sequence spread spectrum(DSSS)signal in underwater acoustic(UWA)communication.Since the dynamic property of the UWA channel and the long duration of DSSS signals result in significant Doppler spread that severely distorts the propagated signal,Doppler tracking and compensation are required.Based on the ultra-wideband property of UWA signal,the Doppler spread not only results in the frequency shift,but also changes the signal duration.Therefore,the accurate estimation of the signal expansion/compression in the time domain can reflect the Doppler spread.Accordingly,we present a Doppler tracking and compensation algorithm for a DSSS signal operating on the correlation output of passband signal at a symbol-by-symbol basis.Note that the carrier frequency of UWA communication is around several kilohertz,and thus the time delay estimation can be performed on the passband to improve the accuracy.Furthermore,the prior information of Doppler limit is used to refine the resolution of delay estimation and achieve sequential estimation.To compensate the correlation magnitude distortion induced by the velocity variation,the local reference signal is selected adaptively based on the filtered Doppler factor.Simulation results demonstrate that the proposed passband Doppler tracking algorithm achieves a superior performance compared with the conventional receiver.