Failure of CD25+ T Cells from Lupus-Prone Mice to Suppress Lupus Glomerulonephritis and Sialoadenitis

Bagavant, Harini; Tung, Kenneth S. K.

doi:10.4049/jimmunol.175.2.944

Cited by 79 publications

(63 citation statements)

References 27 publications

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“…Although Tregs are known to regulate the suppression of the immune system, this property is not very well retained in vivo (47,48,65). Furthermore, it is also known that the presence of the proinflammatory cytokines IL-6, IL-12, and IFN-␥ can influence the stability of Tregs.…”

Section: Discussionmentioning

confidence: 99%

Caerulomycin A Enhances Transforming Growth Factor-β (TGF-β)-Smad3 Protein Signaling by Suppressing Interferon-γ (IFN-γ)-Signal Transducer and Activator of Transcription 1 (STAT1) Protein Signaling to Expand Regulatory T Cells (Tregs)

Gurram¹,

Kujur²,

Maurya³

et al. 2014

Journal of Biological Chemistry

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Background: Caerulomycin A, a known antifungal agent, was explored for its novel immunomodulatory activity. Results: Caerulomycin A supports the generation of Tregs by augmenting the TGF-␤-Smad3 and suppressing the IFN-␥-STAT1 signaling pathways by enhancing SOCS1 expression. Conclusion: Caerulomycin A induces and enhances the Treg population. Significance: Caerulomycin A can be a potent future drug for treating autoimmune diseases by eliciting the generation of Tregs.

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Section: Discussionmentioning

confidence: 99%

Caerulomycin A Enhances Transforming Growth Factor-β (TGF-β)-Smad3 Protein Signaling by Suppressing Interferon-γ (IFN-γ)-Signal Transducer and Activator of Transcription 1 (STAT1) Protein Signaling to Expand Regulatory T Cells (Tregs)

Gurram¹,

Kujur²,

Maurya³

et al. 2014

Journal of Biological Chemistry

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“…These authors also reported that prostatitis was detected in 73% of Tx-3 males of another lupus-prone mouse strain (NZM2328). 108 It has been also shown that the transfer of 1 million CD25 þ T cells to Tx-3 NZM2328 mice completely suppressed prostatitis. In summary, these data strongly suggest the role of T regulatory cells in this model of prostate inflammation.…”

Section: T Regulatory Cell Depleted Mouse Modelmentioning

confidence: 96%

Experimental rodent models of prostatitis: limitations and potential

Vykhovanets

Resnick

MacLennan

et al. 2007

Prostate Cancer Prostatic Dis

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Prostatitis is a polyetiological inflammation of the prostate gland in men characterized by pelvic pain, irritative voiding symptoms, and sexual dysfunction. Histologically prostatitis is characterized by poly-and mononuclear cell infiltrates (neutrophils, lymphocytes, macrophages and plasma cells) in the stromal connective tissue around the acini or ducts. Prostatitis is an important worldwide health problem in men. The pathogenesis and diagnostic criteria for the condition are obscure, with the result that the development of management programs for this condition has been hindered. Animal model(s) might be useful in elucidating mechanisms involved in the molecular pathogenesis of chronic nonbacterial prostatitis and chronic pelvic pain syndrome. Given that prostatitis might have a multifactorial etiology, several animal models with unique features may prove helpful. This review examines a number of experimental rodent models of prostatitis and evaluates their advantages and limitations.

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“…Blocking antibodies for IFN␣, IL-6, tumor necrosis factor ␣ (TNF␣), or IgG1 isotype control (10 g/ml each) were added at the beginning of culture. After 72 hours, 3 H-thymidine incorporation (left) and the percentage inhibition of proliferation (right) were determined. Values are the mean and SEM of 3 independent experiments except for IL-6 and TNF␣ neutralization, which represent only 1 experiment.…”

Section: Contribution Of Ifn␣ Derived From Apcs Obtained From Sle Patmentioning

confidence: 99%

“…Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to self antigens, which is followed by the activation and expansion of autoreactive lymphocytes and the production of various autoantibodies, which are mainly responsible for injury to multiple organ systems. Lupus-prone mice in which the entire CD4ϩ,CD25ϩ Treg cell population has been experimentally depleted by thymectomy have enhanced expansion of autoreactive T cells and accelerated autoantibody production (3). Conversely, supplementation of the CD4ϩ,CD25ϩ Treg cell population isolated from syngeneic normal mice has been shown to effectively abrogate the development of autoimmune disease (3), as has treatment with in vitro-expanded Treg cells (4) or transforming growth factor ␤-generated Treg cells (5).…”

mentioning

confidence: 99%

Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon‐α–producing antigen‐presenting cells

Yan¹,

Ye²,

Chen³

et al. 2008

Arthritis & Rheumatism

165

129

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Objective. To explore whether there are extrinsic factors that impair the suppressive function of CD4؉,CD25؉ regulatory T cells in patients with untreated active systemic lupus erythematosus (SLE).Methods. We studied 15 patients with untreated active SLE, 10 patients with SLE in remission, and 15 healthy control subjects. Percentages of CD4؉,CD25؉, FoxP3؉ Treg cells and levels of forkhead box P3 (FoxP3) protein were analyzed by flow cytometry. Expression of messenger RNA (mRNA) for FoxP3 in purified Treg cell populations was assessed by real-time polymerase chain reaction analysis. Experiments examining Treg cell function in SLE were designed to distinguish primary from secondary T cell dysfunction. Levels of interferon-␣ (IFN␣) in supernatants from the function assays were determined with an IFN-stimulated response element-luciferase reporter assay.Results. The percentage of CD4؉,CD25؉, FoxP3؉ cells in peripheral blood was significantly increased in SLE patients as compared with controls (mean ؎ SEM 9.11 ؎ 0.73% versus 4.78 ؎ 0.43%; P < 0.0001). We found no difference in FoxP3 expression at either the mRNA or protein level in any CD4؉,CD25؉ T cell subset from SLE patients as compared with controls. Antigen-presenting cells (APCs) from SLE patients were responsible for decreased Treg cell activity and could also render dysfunctional Treg cells from healthy control subjects. CD4؉,CD25؉ Treg cells from SLE patients exhibited normal suppressive activity when cultured with APCs from healthy controls. A partial Treg cell blockade effect was induced by the high levels of IFN␣ derived from SLE patient APCs.Conclusion. We suggest that blockade of Treg cell-mediated suppression by IFN␣-producing APCs in SLE patients may contribute to a pathogenic loss of peripheral tolerance in this disease.

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Failure of CD25+ T Cells from Lupus-Prone Mice to Suppress Lupus Glomerulonephritis and Sialoadenitis

Cited by 79 publications

References 27 publications

Caerulomycin A Enhances Transforming Growth Factor-β (TGF-β)-Smad3 Protein Signaling by Suppressing Interferon-γ (IFN-γ)-Signal Transducer and Activator of Transcription 1 (STAT1) Protein Signaling to Expand Regulatory T Cells (Tregs)

Caerulomycin A Enhances Transforming Growth Factor-β (TGF-β)-Smad3 Protein Signaling by Suppressing Interferon-γ (IFN-γ)-Signal Transducer and Activator of Transcription 1 (STAT1) Protein Signaling to Expand Regulatory T Cells (Tregs)

Experimental rodent models of prostatitis: limitations and potential

Dysfunctional CD4+,CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon‐α–producing antigen‐presenting cells

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