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Lupus nephritis (LN) is a significant cause of various acute and chronic renal diseases, which can eventually lead to end-stage renal disease. The pathogenic mechanisms of LN are characterized by abnormal activation of the immune responses, increased cytokine production, and dysregulation of inflammatory signaling pathways. LN treatment is an important issue in the prevention and treatment of systemic lupus erythematosus. Mesenchymal stem cells (MSCs) have the advantages of immunomodulation, anti-inflammation, and anti-proliferation. These unique properties make MSCs a strong candidate for cell therapy of autoimmune diseases. MSCs can suppress the proliferation of innate and adaptive immune cells, such as natural killer cells (NKs), dendritic cells (DCs), T cells, and B cells. Furthermore, MSCs suppress the functions of various immune cells, such as the cytotoxicity of T cells and NKs, maturation and antibody secretion of B cells, maturation and antigen presentation of DCs, and inhibition of cytokine secretion, such as interleukins (ILs), tumor necrosis factor (TNF), and interferons (IFNs) by a variety of immune cells. MSCs can exert immunomodulatory effects in LN through these immune functions to suppress autoimmunity, improve renal pathology, and restore kidney function in lupus mice and LN patients. Herein, we review the role of immune cells and cytokines in the pathogenesis of LN and the mechanisms involved, as well as the progress of research on the immunomodulatory role of MSCs in LN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Luo, Li, Lou, Zhu, Bai, Sun, Lu and Luo.)

Purpose: To investigate the clinical and pathological characteristics of lupus nephritis (LN) patients with serositis and analyse the relationship between serositis and hyperuricemia (HUA) in LN patients in northeast China., Methods: The data of patients with LN diagnosed by renal biopsy in our hospital from April 2013 to May 2020 were retrospectively analyzed. The differences between the non-serositis and serositis groups were compared by t tests and Chi-square test. Factors with P < 0.05 in the univariate analyses were investigated further using binary logistic regression analysis to investigate the independent risk factors of serositis in patients with LN., Results: LN patients with serositis were more likely to have fever, hypertension, neuropsychiatric and hematological involvement than those without serositis (P < 0.05). Compared with the non-serositis group, LN patients with serositis were prone to have HUA, high D-dimer, high triglycerides, and had significant differences in the levels of plasma albumin (Alb), estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate, C-reactive protein, complement C3, 24-h urinary protein, pathological types, pathological score and SLEDAI score. Logistic regression analysis showed that HUA was one of risk factors for serositis in LN patients. The rate of complete remission in LN patients with serositis was significantly lower (P < 0.05) and the rate of no remission and mortality were significantly higher (P < 0.05) than LN patients without serositis., Conclusion: LN patients with serositis had more severe clinical and pathological manifestations, higher systemic lupus erythematosus (SLE) activity and worse prognosis. Hyperuricemia is associated with serositis in LN patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Human placenta-derived mesenchymal stem cells (pMSCs) are considered a good source for cell therapy. The purpose of this study was to observe whether the transplantation of human pMSCs would affect the treatment of lupus nephritis (LN)-prone MRL/lpr mice. Multiple injections (at the 16th, 18th, and 20th week of age) of 1 × 10 6 pMSCs were administered. Urine was collected to evaluate proteinuria and urine creatinine levels. Blood was collected for the measurement of serum antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA) antibody levels. Renal tissues were collected for histological staining and examination by light and electron microscopy quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot. The results confirmed that pMSC treatment reduced the severity of 24-h proteinuria, decreased the production of anti-dsDNA antibodies, and ameliorated renal pathological changes in MRL/lpr mice. Furthermore, pMSCs reduced renal inflammation by inhibiting the expression of nuclear factor kappa B (NF- κ B) and then downregulating the expression of tumor necrosis factor- α (TNF- α ), intercellular cell adhesion molecule-1 (ICAM-1), and plasminogen activator inhibitor-1 (PAI-1). Therefore, our present study demonstrated a protective effect of pMSCs against renal injury and inflammation in MRL/lpr mice.

Mice with chronic graft-versus-host disease (cGVHD) induced by transferring parental BALB/C lymphocytes into (C57BL/6 × BALB/C) F1 (CBF1) hybrids, develop a syndrome characterized by B-cell hyperactivity, autoantibody production, and immune complex-mediated glomerulonephritis. In this model, we evaluated the role of leflunomide on the development of lupus nephritis in system autoimmunity. Daily administration of leflunomide (15 mg/kg/d) from 2 weeks after cGVHD induction can dramatically reduce the production of autoantibodies and immune complex deposition in the kidney, leading to relieved kidney damage and reduced mortality. The therapeutic effect of leflunomide on the lupus-prone mice was partially due to the inhibition of TLR9 signaling pathway, which was an important component of innate immune system.

Lupus nephritis (LN) is a common secondary glomerular disease with diverse clinical manifestations and pathology. We retrospectively analyzed the clinical manifestations and pathology of 82 hospitalized LN patients (73 females and nine males) during February 2004 to February 2009. The mean age at disease onset of male patients was much younger than female patients (27.6 +/- 6.8 vs. 35.5 +/- 13.9). The kidney biopsy showed that more than 50% was IV-type LN. The II- and III-type LN were also common; their clinical manifestations were common in nephritic syndrome and (or) asymptomatic urinary abnormalities, whereas IV- and V-type LN usually presented nephrotic syndrome. Simultaneously, we investigated that the highest incidence rates of anemia and chronic renal failure were observed in IV- and IV + V-type LN. What was more, we found that serum creatinine level was higher; the interstitial involvement was more severe with renal biopsy. The serum creatinine level and renal interstitial lesions were positively correlated. Our study showed that the different pathologic phenotypes of LN were correlated with the specific clinical manifestations. However, the conclusion should be confirmed by large-scale prospective research.