Regulatory B Cells Induce Formation of IL-10-Expressing T Cells in Mice with Autoimmune Neuroinflammation

Pennati, Andrea; Ng, Spencer; Wu, Yayun; Murphy, Jordan; Deng, Jiusheng; Rangaraju, Srikant; Asress, Seneshaw; Blanchfield, Lori; Evavold, Brian D; Galipeau, Jacques

doi:10.1523/jneurosci.1994-16.2016

Cited by 48 publications

(44 citation statements)

References 48 publications

(3 reference statements)

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“…Adoptive transfer of IL‐10 + B cells to chronic collagen‐induced arthritis mice suppressed Th1 differentiation, alleviated arthritis severity, and ameliorated the established disease . In addition, 1 week after in vivo adoptive transfer of IL‐10‐secreting Bregs stimulated with GM‐CSF and IL‐15 fusokine, a marked increase in the proportion of both FoxP3 + T cells and type 1 Tregs was observed in the spleen of EAE mice …”

Section: Regulatory Functions Of B Cells In Transplantationmentioning

confidence: 99%

Regulatory B cells and advances in transplantation

Luo

Wang

et al. 2018

Journal of Leukocyte Biology

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The effects of B cell subsets with regulatory activity on the immune response to an allograft have evoked increasing interest. Here, we summarize the function and signaling of regulatory B cells (Bregs) and their potential effects on transplantation. These cells are able to suppress the immune system directly via ligand–receptor interactions and indirectly by secretion of immunosuppressive cytokines, particularly IL‐10. In experimental animal models, the extensively studied IL‐10‐producing B cells have shown unique therapeutic advantages in the transplant field. In addition, adoptive transfer of B cell subsets with regulatory activity may reveal a new approach to prolonging allograft survival. Recent clinical observations on currently available therapies targeting B cells have revealed that Bregs play an important role in immune tolerance and that these cells are expected to become a new target of immunotherapy for transplant‐related diseases.

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Section: Regulatory Functions Of B Cells In Transplantationmentioning

confidence: 99%

Regulatory B cells and advances in transplantation

Luo

Wang

et al. 2018

Journal of Leukocyte Biology

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“…Stimulating CD46 on T cells can trigger the transformation of Th cells into IL-10 producing Tr1 cells (Kemper et al, 2003;Truscott et al, 2010), immunosuppressive effects, such as the production of IL-10 and the expression of CD25, CTLA-4, PD-1, and LAG3 (Lykken, Candando, & Tedder, 2015;Pennati et al, 2016). Breg cells can also secrete IL-10 in a large amount, thereby promoting the differentiation and proliferation of Tr1 cells (Carter, Rosser, & Mauri, 2012;Pennati et al, 2016;Said, Barut, Mansur, Korkmaz, & Sayi-Yazgan, 2018;Volchenkov et al, 2013). Pennati et al (2016) found that exogenously elevated Breg cells in EAE mice can effectively increase the number and function of Tr1 cells and alleviate disease progression.…”

Section: Tr1 Cells In Msmentioning

confidence: 99%

Decreased number and impaired function of type 1 regulatory T cells in autoimmune diseases

Jia

Zhai

Wang

et al. 2019

Journal Cellular Physiology

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Type 1 regulatory T (Tr1) cell is a special type of T regulatory cells with surface molecular markers such as lymphocyte‐activation gene 3 and CD49b. A key property of Tr1 cells is the capability to produce high‐level interleukin 10 (IL‐10) upon activation, in a FOXP3‐independent manner. The immunosuppressive function of IL‐10 producing Tr1 cells has been extensively studied for many years. Autoimmune diseases (AIDs) are conditions in which the immune system breaks down and starts to attack the body. AIDs include inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis (MS), type 1 diabetes mellitus, Greaves' disease, and so forth. In recent years, more and more studies have documented that the number of Tr1 cells is decreased and the function is inhibited in a variety of AIDs, among which MS is the most widely studied. The protocol for engineering Tr1 cell therapy has been established and is gradually being used in clinical practice in recent years. Tr1 cell therapy has been proven to be safe and effective, but it is mainly involved in myeloid leukemia, graft versus host disease currently. Its therapeutic role in AIDs still needs to be further explored. In this study, we will summarize the research advances of Tr1 cells in AIDs, which will provide useful information for treating AIDs through Tr1 cell therapy in the future.

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“…Mesenchymal stromal cells were isolated from the bone marrow of Lewis or BN rats similar to the methods of Galipeau. 42 - 45 Briefly, 6- to 8-week-old rats were euthanized by CO 2 , and the muscle was dissected from the femurs and tibiae immediately, leaving isolated bone. The tips of the bones were shaved off with a rongeur.…”

Section: Methodsmentioning

confidence: 99%

Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells

Zhang

Wilson

Chinnadurai

et al. 2018

Transplantation Direct

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BackgroundWe hypothesized that immunomodulatory properties of mesenchymal stromal cells (MSC) may be considered for desensitization.MethodsAutologous or allogeneic bone marrow derived MSC were infused via tail vein at 0.5 M (0.5 × 106), 1 M, or 2 M cells/dose on days −2, 3, 6, 9, 12 (prevention) or 14, 17, 20, 23, 26 (treatment) relative to transfusion in a Brown Norway to Lewis rat model (10 groups total, n = 6 per group).ResultsAt 4 weeks, pooled analyses demonstrated that autologous and allogeneic MSC were equally effective in reducing IgG1 and IgG2a de novo donor-specific antibody (dnDSA, P < 0.001). Dose-response studies indicated that moderate-dose MSC (5 M total) was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). Time course studies determined that preventive and treatment strategies were equally effective in reducing IgG1 and IgG2a dnDSA (P ≤ 0.01). However, individual group analyses determined that moderate-dose (5 M) treatment with autologous MSC was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). In this group, dnDSA decreased after 1 week of treatment; regulatory B cells increased in the spleen and peripheral blood mononuclear cells; and transitional B cells increased in the spleen, peripheral blood mononuclear cells, and bone marrow (P < 0.05 for all).ConclusionsOur findings indicate that autologous MSC prevent transfusion-elicited sensitization and upregulate transitional, and regulatory B cells. Additional studies are needed to determine the biological relevance of these changes after kidney transplantation.

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Regulatory B Cells Induce Formation of IL-10-Expressing T Cells in Mice with Autoimmune Neuroinflammation

Cited by 48 publications

References 48 publications

Regulatory B cells and advances in transplantation

Regulatory B cells and advances in transplantation

Decreased number and impaired function of type 1 regulatory T cells in autoimmune diseases

Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells

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