The Role of Regulatory B cells in Kidney Diseases

Wang, Long; Zhang, Hedong; Yuan, Wenjia; Lan, Gongbin; Lin, Zijia; Peng, Longkai; Dai, Helong

doi:10.3389/fimmu.2021.683926

Cited by 11 publications

(10 citation statements)

References 154 publications

(187 reference statements)

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“…However, there is a lack of unique defining human Breg markers that limits their clinical application. The canonical view on human Breg was originally focused on IL-10 as the gold standard to discern regulatory B cells, however, Breg research has diversified in recent years, transitioning from the study of Breg as a single subset, to the association of different markers to Breg across all B cell subsets (5)(6)(7)(8).…”

Section: Discussionmentioning

confidence: 99%

“…A specific subset of B lymphocytes, known as regulatory B cells (Breg), can modulate the immune response by suppressing T cell activation and proliferation, inducing differentiation of regulatory T cells, and producing immunomodulatory factors such as IL-10 (5). Breg are essential in the maintenance of immune homeostasis and immunological tolerance, but despite extensive discussion and research done in recent years (5)(6)(7)(8), several drawbacks including the lack of unique defining markers, and the heterogeneity across experimental settings and animal models are undermining their therapeutic potential. Regarding the first, the general consensus on human studies is that IL-10 identifies Bregs in vivo and is crucial to exert their immunomodulatory role.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stromal cells induced regulatory B cells are enriched in extracellular matrix genes and IL-10 independent modulators

et al. 2022

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Regulatory B cells (Breg) are essential players in tolerance and immune homeostasis. However, lack of specific Breg markers limit their potential in clinical settings. Mesenchymal stromal cells (MSC) modulate B cell responses and are described to induce Breg in vitro. The aim of this work was to characterize MSC induced Breg (iBreg) and identify specific Breg biomarkers by RNAseq. After 7-day coculture with adipose tissue-derived MSC, B cells were enriched in transitional B cell populations, with increased expression and secretion of IL-10 and no TNFα. In addition, iBreg showed potential to modulate T cell proliferation at 2 to 1 cell ratios and their phenotype remained stable for 72h. RNAseq analysis of sorted IL-10 positive and negative iBreg populations identified over 1500 differentially expressed genes (DEG) among both populations. Analysis of biological processes of DEG highlighted an enrichment of immune regulation and extracellular matrix genes in IL-10- iBreg populations, while IL-10+ iBreg DEG were mostly associated with cell activation. This was supported by T cells modulation assays performed in the presence of anti-IL-10 neutralizing antibodies showing the non-essential role of IL-10 in the immunomodulatory capacity of iBregs on T cells. However, based on RNAseq results we explored the role of TGF-β and found out that it plays a major role on iBreg induction and iBreg immunomodulatory properties. Therefore, we report that MSC induce B cell populations characterized by the generation of extracellular matrix and immune modulation independently of IL-10.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal cells induced regulatory B cells are enriched in extracellular matrix genes and IL-10 independent modulators

et al. 2022

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“…CY reduces the absolute number of T lymphocytes and B lymphocytes, especially for B lymphocytes in the early stage. In rodents, CY can mediate lymphocyte loss, which is mainly manifested in the reduction of lymphoid follicles and germinal centers [ 28 , 29 ]. Generally, the loss reaches the peak three days after cyclophosphamide treatment, and the cell density can return to the original level seven days later [ 28 , 30 ].…”

Section: Immunopharmacological Mechanism Of Cy In Ln Treatmentmentioning

confidence: 99%

Revisited Cyclophosphamide in the Treatment of Lupus Nephritis

Quan

Chen

Liang

et al. 2022

BioMed Research International

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Lupus nephritis (LN) is the most common serious complication of systemic lupus erythematosus (SLE). The pathogenesis of LN is complex, and the majority causes of LN are the renal deposition of circulating or/and in situ-formed immune complexes. These immune complexes trigger glomerular and tubulointerstitial inflammation, which finally leads to proteinuria and loss of renal function. Despite the emergence of new biological agents, cyclophosphamide (CY), an alkylating agent, is still the first-line drug widely used to treat patients with severe LN. In this review, we outline the application history, molecular structure, and pharmacokinetics of CY in the treatment of LN. We also detail its latest known immunopharmacological mechanisms, with a focus on supplemental regulation and inhibition of CD4 and CD8 positive T cells, differences in the use of various guidelines, and the combination with other drugs. The side effects of CY are also mentioned in this review.

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“…Despite essential roles in modulating several diseases, Bregs so far are not known to have a unique or exclusive marker that defines them as a population, but they constitute a heterogeneous cell population that possess a regulatory phenotype and can be found at different stages of B-cell development as reviewed in ( Rosser and Mauri, 2015 ; Oleinika et al, 2019 ; Long et al, 2021 ). However, several markers have been proposed as enriched or identifiers of Breg populations.…”

Section: Introductionmentioning

confidence: 99%

“…Since the emergence of these breakthrough results in 2010, the effect of Breg on the development of tolerance has been described several times as reviewed in ( Peng et al, 2018 ; Cherukuri et al, 2021 ; Long et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Regulatory B Cell Therapy in Kidney Transplantation

2021

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In the context of kidney injury, the role of Bregs is gaining interest. In a number of autoimmune diseases, the number and/or the function of Bregs has been shown to be impaired or downregulated, therefore restoring their balance might be a potential therapeutic tool. Moreover, in the context of kidney transplantation their upregulation has been linked to tolerance. However, a specific marker or set of markers that define Bregs as a unique cell subset has not been found and otherwise multiple phenotypes of Bregs have been studied. A quest on the proper markers and induction mechanisms is now the goal of many researchers. Here we summarize the most recent evidence on the role of Bregs in kidney disease by describing the relevance of in vitro and in vivo Bregs induction as well as the potential use of Bregs as cell therapy agents in kidney transplantation.

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The Role of Regulatory B cells in Kidney Diseases

Cited by 11 publications

References 154 publications

Mesenchymal stromal cells induced regulatory B cells are enriched in extracellular matrix genes and IL-10 independent modulators

Mesenchymal stromal cells induced regulatory B cells are enriched in extracellular matrix genes and IL-10 independent modulators

Revisited Cyclophosphamide in the Treatment of Lupus Nephritis

Regulatory B Cell Therapy in Kidney Transplantation

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