Exacerbated experimental arthritis in Wiskott–Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells

Bouma, Gerben; Carter, Natalie A.; Recher, Mike; Malinova, Dessislava; Adriani, Marsilio; Notarangelo, Luigi D.; Burns, Siobhan O.; Mauri, Claudia; Thrasher, Adrian J.

doi:10.1002/eji.201344245

Cited by 23 publications

(25 citation statements)

References 47 publications

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“…Regulatory B cells suppress the activation and differentiation of CD4 + , CD8 + , and NKT cells primarily by releasing anti-inflammatory cytokines IL-10 and TGF-β (Mauri and Ehrenstein 2008). B10 cells can also promote Foxp3 + Treg cell induction and inhibit Th1 and Th17 cell proliferation during acute inflammation (Bouma et al 2014). …”

Section: Introductionmentioning

confidence: 98%

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells

Fang

Xian

et al. 2015

Parasitol Res

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A distinct subset of B cells, also known as regulatory B cells, can negatively regulate T cell immune responses, but the role of these cells in schistosomiasis has not been clarified. Soluble egg antigen (SEA) and soluble adult worm antigen preparation (SWAP), which are two important antigen sources during Schistosoma japonicum infection, both can induce Th1, Th2, Th17, and Treg cells and the corresponding cytokines. However, whether they can induce the production of regulatory B cells and the regulatory function of schistosome-induced regulatory B cells remains unclear. In our studies, we first analyzed the production of regulatory B cells stimulated by SEA or SWAP using flow cytometry and enzyme-linked immunosorbent assay, and observed these cells in mice immunized by SEA or SWAP. Then, B10 cells sorted by MicroBeads were co-cultured with CD4(+) T cells, and the proportion of Treg cells were detected. At the same time, the IFN-γ, IL-4, and IL-17 levels in the culture supernatant were measured. The results showed that B10 cells were preferentially induced by SEA in vitro, and B10 could also be induced in mice immunized by SEA. SEA-induced B10 cells promoted the expansion of regulatory T cells and induced IL-4 secretion, but inhibited IL-17 production. These findings reveal that the generation of B10 cells is determined by parasitic antigen, and suggest the function of B10 cell induced by SEA. This study significantly contributes to the understanding of the immune regulatory role in schistosomiasis and may help protect hosts from infection.

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Section: Introductionmentioning

confidence: 98%

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells

Fang

Xian

et al. 2015

Parasitol Res

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“…It has been shown that Breg deficiency and dysfunction is associated with multiple inflammatory disorders, such as autoimmune thrombocytopenia, ulcerative colitis, systemic lupus erythematosus, and experimental arthritis . Therefore, in this study, we examined the Breg cells in human patients with atherosclerosis and CAD.…”

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confidence: 99%

Tim‐1⁺ B cells suppress T cell interferon‐gamma production and promote Foxp3 expression, but have impaired regulatory function in coronary artery disease

Lin

et al. 2017

APMIS

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Atherosclerosis and its associated coronary artery disease (CAD) represent another chronic low-grade inflammatory disorder. Regulatory B cells (Bregs) possess essential functions in maintaining peripheral tolerance and inhibiting pathogenic inflammation through IL-10. Here, we investigated one subset of Bregs, Tim-1 B cell, and its role in atherosclerosis and CAD patients. In healthy individuals, IL-10-producing B cells were predominantly found in the Tim-1 B cells. Upon stimulation of the B cell receptor (BCR) and Toll-like receptor 9 (TLR-9) by anti-BCR antibodies and CpG, respectively, the Tim-1 B cells could further upregulate IL-10 expression. In contrast, the Tim-1 B cells were present at normal frequency in CAD patients, but showed impaired capacity to upregulate IL-10 with or without BCR + CpG stimulation. The stimulated Tim-1 B cells from healthy individuals also suppressed expression of interferon gamma (IFN-γ), an atherogenic cytokine in T cells, in an IL-10-dependent fashion, and strongly promoted the expression of Foxp3 in naive CD4 CD45RO T cells. In contrast, the Tim-1 B cells from CAD patients were unable to suppress IFN-γ secretion, and only minimally increased the expression of Foxp3 in naive CD4 CD45RO T cells. Despite this, the frequency of Tim-1 B cells in the atherosclerotic lesions from CAD patients was inversely correlated with the frequency of IFN-γ-expressing T cells. Together, these results demonstrated that CAD patients presented an inflammatory disorder in regulatory B cells, which could be used as a therapeutic target.

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“…5 A recent study reported an increase in Th17 cells in WAS knockout (KO) mice, which was associated with exacerbated arthritis. 6 However, T follicular helper (Tfh) cells, a CD4…”

Section: Introductionmentioning

confidence: 99%

Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome

Zhang

Dai

et al. 2016

Blood

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Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific regulator of actin nucleation. Wiskott-Aldrich syndrome (WAS) patients show immunodeficiencies, most of which have been attributed to defective T-cell functions. T follicular helper (Tfh) cells are the major CD4+ T-cell subset with specialized B-cell helper capabilities. Aberrant Tfh cells activities are involved in immunopathologies such as autoimmunity, immunodeficiencies, and lymphomas. We found that in WAS patients, the number of circulating Tfh cells was significantly reduced due to reduced proliferation and increased apoptosis, and Tfh cells were Th2 and Th17 polarized. The expression of inducible costimulator (ICOS) in circulating Tfh cells was higher in WAS patients than in controls. BCL6 expression was decreased in total CD4+ T and Tfh cells of WAS patients. Mirroring the results in patients, the frequency of Tfh cells in WAS knockout (KO) mice was decreased, as was the frequency of BCL6+ Tfh cells, but the frequency of ICOS+ Tfh cells was increased. Using WAS chimera mice, we found that the number of ICOS+ Tfh cells was decreased in WAS chimera mice, indicating that the increase in ICOS+ Tfh cells in WAS KO mice was cell extrinsic. The data from in vivo CD4+ naive T-cell adoptive transfer mice as well as in vitro coculture of naive B and Tfh cells showed that the defective function of WASp-deficient Tfh cells was T-cell intrinsic. Consistent findings in both WAS patients and WAS KO mice suggested an essential role for WASp in the development and memory response of Tfh cells and that WASp deficiency causes a deficient differentiation defect in Tfh cells by downregulating the transcription level of BCL6.

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Exacerbated experimental arthritis in Wiskott–Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells

Cited by 23 publications

References 47 publications

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells

Tim‐1⁺ B cells suppress T cell interferon‐gamma production and promote Foxp3 expression, but have impaired regulatory function in coronary artery disease

Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome

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Exacerbated experimental arthritis in Wiskott–Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells

Cited by 23 publications

References 47 publications

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells

Tim‐1+ B cells suppress T cell interferon‐gamma production and promote Foxp3 expression, but have impaired regulatory function in coronary artery disease

Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome

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Tim‐1⁺ B cells suppress T cell interferon‐gamma production and promote Foxp3 expression, but have impaired regulatory function in coronary artery disease