Immune Modulatory Effect of Thalidomide on T Cells

Kim, B.S.; Kim, J.Y.; Lee, Jae Geun; Cho, Y.; Huh, Kyu Ha; Kim, M.S.; Kim, Y.S.

doi:10.1016/j.transproceed.2014.12.038

Cited by 14 publications

(20 citation statements)

References 13 publications

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“…TM possesses an immunosuppressive function, which may be useful following transplantation, and not only suppresses, but modulates the immune response by regulating key immune‐modulatory molecules, including nuclear factor‐ κ B and pro‐inflammatory cytokines such as tumour necrosis factor‐ α (TNF‐ α ), interferon‐ γ (IFN‐ γ ), interleukin (IL)‐6, IL‐10, IL‐12, and cyclooxygenase 2 . Our previous study further substantiated the immunomodulatory effects of TM, demonstrating that TM selectively suppresses effector T (Teff) cells among total CD4 + T cells . We also found that the immunomodulatory effect of TM was potentiated with glucocorticoid (GC)‐combined treatment .…”

Section: Introductionsupporting

confidence: 56%

“…Shortly after its introduction in the 1950s, thalidomide (TM) was banned due to its tragic teratogenic effect; however, as recent studies revealed its anti‐angiogenic and anti‐inflammatory effects, TM has regained attention in the fields of cancer and autoimmune diseases . TM possesses an immunosuppressive function, which may be useful following transplantation, and not only suppresses, but modulates the immune response by regulating key immune‐modulatory molecules, including nuclear factor‐ κ B and pro‐inflammatory cytokines such as tumour necrosis factor‐ α (TNF‐ α ), interferon‐ γ (IFN‐ γ ), interleukin (IL)‐6, IL‐10, IL‐12, and cyclooxygenase 2 . Our previous study further substantiated the immunomodulatory effects of TM, demonstrating that TM selectively suppresses effector T (Teff) cells among total CD4 + T cells .…”

Section: Introductionmentioning

confidence: 99%

“…Interactions of TNFSF and TNFRSF play critical roles in regulating both pro‐inflammatory and anti‐inflammatory responses in autoimmune diseases . Their interactions transmit co‐stimulatory signals and regulate a broad range of immune activities by triggering, suppressing, or activating immune cell functions …”

Section: Introductionmentioning

confidence: 99%

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Enhanced immune‐modulatory effects of thalidomide and dexamethasone co‐treatment on T cell subsets

et al. 2017

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Thalidomide (TM) has been reported to have anti-cancer and anti-inflammatory properties, and dexamethasone (DX) is known to reduce inflammation and inhibit production of inflammatory cytokines. Many studies have reported that combinatorial therapy with TM and DX is clinically used to treat multiple myeloma and lupus nephritis, but the mechanism responsible for its effects has not been elucidated. In this study, we determined that TM and DX co-treatment had an enhanced immune-modulatory effect on T cells through regulating the expression of co-stimulatory molecules. Splenic naive T cells from C57BL/6 mice were sort-purified and cultured for CD4 T cell proliferation and regulatory T (Treg) cell conversion in the presence of TM and/or DX. Following incubation with the drugs, cells were collected and OX40, 4-1BB, and glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) expression was quantified by flow cytometry. TM (1 or 10 μm) decreased CD4 T cell proliferation in a dose-dependent manner, whereas TM/DX (0·1 or 1 nm) co-treatment further decreased proliferation. Treg cell populations were preserved following drug treatment. Furthermore, expression of co-stimulatory molecules decreased upon TM/DX co-treatment in effector T (Teff) cells and was preserved in Treg cells. Splenic CD4 T cells isolated from TM- and DX-treated mice exhibited the same patterns of Teff and Treg cell populations as observed in vitro. Considering the selective effect of TM on different T cell subsets, we suggest that TM may play an immunomodulatory role and that TM/DX combinatorial treatment could further enhance these immunomodulatory effects by regulating GITR, OX40, and 4-1BB expression in CD4 T cells.

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Section: Introductionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

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Enhanced immune‐modulatory effects of thalidomide and dexamethasone co‐treatment on T cell subsets

et al. 2017

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“…Treatment with thalidomide may increase the neutrophil numbers, at least partially through differentially modulating the surface expression of markers CD18 and CD44 by the neutrophils in the bone marrow and the spleen (227). Thalidomide treatment may also affect T-cell functions by suppressing CD4 + T-cell proliferation while increasing their conversion to CD4 + FoxP3 + Tregs (228). Moreover, thalidomide treatment may reduce cytokine levels (229).…”

Section: Methodological Considerations Of the Studies Included In Thementioning

confidence: 99%

A Systematic Review of Immunological Studies of Erythema Nodosum Leprosum

2017

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Erythema nodosum leprosum (ENL) is a painful inflammatory complication of leprosy occurring in 50% of lepromatous leprosy patients and 5–10% of borderline lepromatous patients. It is a significant cause of economic hardship, morbidity and mortality in leprosy patients. Our understanding of the causes of ENL is limited. We performed a systematic review of the published literature and critically evaluated the evidence for the role of neutrophils, immune complexes (ICs), T-cells, cytokines, and other immunological factors that could contribute to the development of ENL. Searches of the literature were performed in PubMed. Studies, independent of published date, using samples from patients with ENL were included. The search revealed more than 20,000 articles of which 146 eligible studies were included in this systematic review. The studies demonstrate that ENL may be associated with a neutrophilic infiltrate, but it is not clear whether it is an IC-mediated process or that the presence of ICs is an epiphenomenon. Increased levels of tumor necrosis factor-α and other pro-inflammatory cytokines support the role of this cytokine in the inflammatory phase of ENL but not necessarily the initiation. T-cell subsets appear to be important in ENL since multiple studies report an increased CD4+/CD8+ ratio in both skin and peripheral blood of patients with ENL. Microarray data have identified new molecules and whole pathophysiological pathways associated with ENL and provides new insights into the pathogenesis of ENL. Studies of ENL are often difficult to compare due to a lack of case definitions, treatment status, and timing of sampling as well as the use of different laboratory techniques. A standardized approach to some of these issues would be useful. ENL appears to be a complex interaction of various aspects of the immune system. Rigorous clinical descriptions of well-defined cohorts of patients and a systems biology approach using available technologies such as genomics, epigenomics, transcriptomics, and proteomics could yield greater understanding of the condition.

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“…Payvandi et al (35) demonstrated that IMiDs increased IL-2 production in stimulated T cells via enhancing PKC-θ activation and DNA-binding activity of activated protein-1 (AP-1). In addition to conventional T cells, regulatory T cells (Tregs) are a group of immunosuppressive T cells that function in self-tolerance and the immune response (36). Inhibition of Tregs by lenalidomide (Revlimid; CC-5013) and pomalidomide (CC-4047) via decreasing the expression of forkhead box P3 (FoxP3) was observed in a preclinical study (32).…”

Section: T Cell and Natural Killer (Nk) Cell Functionsmentioning

confidence: 99%

Thalidomide and its analogues: A review of the potential for immunomodulation of fibrosis diseases and opthalmopathy (Review)

et al. 2017

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Abstract. The US Food and Drug Administration approved thalidomide and its analogues for the treatment of erythema nodosum leprosum, in spite of the notoriety of reports of severe birth defects in the middle of the last century. As immunomodulatory drugs, thalidomide and its analogues have been used to effectively treat various diseases. In the present review, preclinical data about the effects of thalidomide and its analogues on the immune system are integrated, including the effects of cytokines on transdifferentiation, the anti-inflammatory effect, immune cell function regulation and angiogenesis. The present review also investigates the latest developments of thalidomide as a therapeutic option for the treatment of idiopathic pulmonary fibrosis, skin fibrosis, and ophthalmopathies.

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Immune Modulatory Effect of Thalidomide on T Cells

Cited by 14 publications

References 13 publications

Enhanced immune‐modulatory effects of thalidomide and dexamethasone co‐treatment on T cell subsets

Enhanced immune‐modulatory effects of thalidomide and dexamethasone co‐treatment on T cell subsets

A Systematic Review of Immunological Studies of Erythema Nodosum Leprosum

Thalidomide and its analogues: A review of the potential for immunomodulation of fibrosis diseases and opthalmopathy (Review)

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