Bcl-xL is required for the development of functional regulatory CD4 cells in lupus-afflicted mice following treatment with a tolerogenic peptide

Sharabi, Amir; Lapter, Smadar; Mozes, Edna

doi:10.1016/j.jaut.2009.06.002

Cited by 25 publications

(21 citation statements)

References 48 publications

(59 reference statements)

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“…Because this information was not mentioned in the article by Haque and colleagues [1] and because the results presented in their article confirm our previous studies [2-5], we think that it is important, scientifically and ethically, to acknowledge these data.…”

mentioning

confidence: 50%

“…Indications for a potential role of Bcl-xL in the development of functional Tregs were first described by our group, and the results of studies supporting this notion were published in numerous journals (for example, [2-5]). Because this information was not mentioned in the article by Haque and colleagues [1] and because the results presented in their article confirm our previous studies [2-5], we think that it is important, scientifically and ethically, to acknowledge these data.…”

mentioning

confidence: 99%

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Bcl-xL affects the development of functional CD4 Tregs

Sharabi

Mozes

2010

Arthritis Res Ther

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confidence: 50%

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confidence: 99%

Bcl-xL affects the development of functional CD4 Tregs

Sharabi

Mozes

2010

Arthritis Res Ther

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“…Elevated levels of Bcl-xL have been shown in patients and mice with MM (33,34), which influenced both the development of the disease and the response to treatment. Furthermore, Bcl-xL has been implicated in the development of Tregs (35). In addition, the expression of CTLA-4 in CD4 + CD25…”

Section: Discussionmentioning

confidence: 99%

Chemoimmunotherapy Reduces the Progression of Multiple Myeloma in a Mouse Model

Sharabi

Laronne-Bar-On

Meshorer

et al. 2010

Cancer Prevention Research

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Multiple myeloma (MM) is a B-cell malignancy characterized by clonal proliferation of malignant plasma cells in the bone marrow. Recently, we showed a correlation between increased ratios of functional regulatory T cells (Treg) and disease progression in a unique mouse model that mimics the human disease. Cyclophosphamide (CYC) is a cytotoxic alkylating agent widely used in chemotherapeutic regimens. Low-dose CYC was previously reported to selectively reduce Treg levels and to contribute to immunostimulation. Our objectives were (a) to determine whether treatment using a low-dose CYC could reduce MM progression and (b) to further characterize the modes of action underlying these effects. We found that both low-and high-dose CYC given to sick mice with hind limb paralysis resulted in the disappearance of the paralysis, the replacement of plasma tumor cells in the bone marrow by normal cell populations, and a significant prolongation of survival. However, only low-dose CYC treatment decreased the incidence of MM. Low-dose CYC rendered Tregs susceptible to apoptosis because of the downregulation of Bcl-xL and CTLA-4 in these cells, and a decreased production of interleukin 2 by effector CD4 cells. Moreover, using this treatment, we noted the recovery of IFN-γ-producing natural killer T cells and maturation of dendritic cells. Treatment of tumor-bearing mice with repeated administrations of low-dose CYC at longer time intervals (coinciding with the blocked renewal of Tregs) resulted in reduced tumor load, and the prevention or delay of disease recurrence, thereby breaking immune tolerance against MM tumor cells. Cancer Prev Res; 3(10); 1265-76. ©2010 AACR.

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“…β-catenin promoted the survival of Treg cells in vitro without changing their anergic state or suppressive function by regulating expression of anti-apoptotic bcl-xL (89). Indeed, bcl-xL is involved in the development and function of Treg cells by inducing the expression of Foxp3, CTLA-4, TGF-β, and repressing the programed death receptor-1 (PD-I) expression (90, 91). Foxp3 and bcl-xL cooperatively promote the survival of Treg cells and prevent arthritis development because of the increased survival of Treg cells (80).…”

Section: Advantages and Disadvantages For The Use Of Treg Cell-based mentioning

confidence: 99%

Utilizing Regulatory T Cells Against Rheumatoid Arthritis

et al. 2014

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Regulatory T (Treg) cells are essential for normal immune surveillance systems, and their dysfunction leads to development of diseases, such as autoimmune disorders. CD4+CD25+ Treg cells are well-known suppressive cells, which express the transcription factor Foxp3, are indispensable for the maintenance of immune self-tolerance and homeostasis by suppressing aberrant or excessive immune response. Other Foxp3− Treg cells include Tr1, Th3, CD8+CD28−/−, and Qa1-restricted T cells; however, the contribution of these Treg cells to self-tolerance, immune homeostasis as well as preventing autoimmunity is not well defined. Here, we discuss the phenotypes and function of Foxp3+ Treg cells and the potential use of such Treg cells against rheumatoid arthritis (RA). Of note, even though most expanded populations of Foxp3+ Treg cells exhibit suppressive activity, tissue-associated or antigen-specific Treg cells appear superior in suppressing local autoimmune disorders such as RA. In addition, utilizing tissue-associated Foxp3+ Treg cells from stem cells may stable Foxp3 expression and avoid induction of a potentially detrimental systemic immunosuppression.

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Bcl-xL is required for the development of functional regulatory CD4 cells in lupus-afflicted mice following treatment with a tolerogenic peptide

Cited by 25 publications

References 48 publications

Bcl-xL affects the development of functional CD4 Tregs

Bcl-xL affects the development of functional CD4 Tregs

Chemoimmunotherapy Reduces the Progression of Multiple Myeloma in a Mouse Model

Utilizing Regulatory T Cells Against Rheumatoid Arthritis

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