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Transitional Immature Regulatory B Cells and Regulatory Cytokines Can Discriminate Chronic Antibody-Mediated Rejection From Stable Graft Function Publisher Pubmed



Salehi S1, 2 ; Shahi A1 ; Afzali S1 ; Keshtkar AA3 ; Farashi Bonab S1 ; Soleymanian T4 ; Ansaripour B1 ; Amirzargar AA1
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Tehran University of Medical Science, Tehran, Iran
  2. 2. Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Health Sciences Education Development, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Nephrology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: International Immunopharmacology Published:2020


Abstract

Background: The balance between inflammatory and anti-inflammatory responses of the immune system has been demonstrated to determine the fate of transplanted allografts. Here we analyzed CD19+CD24hiCD38hi immature transitional regulatory B (TRB) cells, as well as the gene and protein levels of interleukin (IL)-10 and transforming growth factor (TGF)-β in the three separate groups, include of stable transplanted subjects, chronic antibody-mediated rejection (cAMR) patients, and healthy individuals. Method: Peripheral blood mononuclear cells (PBMCs) from stable subjects (n = 36), cAMR patients (n = 36) and healthy controls (n = 18) were isolated. Flowcytometry was performed for CD19, CD24, and CD38 surface markers. ELISA and quantitative real-time PCR were performed for IL-10 and TGF-β cytokines. Result: The percentages of immature TRB cells were significantly decrease in cAMR patients (0.98%) versus stable recipients (2.81%) and healthy subjects (4.03%) (P = 0.001 and P < 0.001, respectively). Total lymphocytes, circulating B cells, memory and mature subsets of B cells did not show any significant difference between the groups. TGF-β mRNA was 3-fold upregulated in the cAMR group compared to stable patients (P < 0.001.), but without significant alteration at the protein level. Also, long-term survival renal transplant recipients had a higher protein but not mRNA levels of IL-10 than short-term survival renal transplant recipients. Conclusion: It seems that immature TRB cell subpopulation might be a crucial regulator of immune system response and plays an important role in determining the transplantation outcome. Furthermore, immunosuppressive IL-10 and TGF-β cytokines might act as a double sword and can exhibit either pathogenic or protective effects against allograft. © 2020
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