Th17 Cells in Multiple Sclerosis Express Higher Levels of JAK2, Which Increases Their Surface Expression of IFN-γR2

Conti, Laura; Palma, Raffaele De; Rolla, Simona; Boselli, Daniela; Rodolico, Gabriella; Kaur, Surinder; Silvennoinen, Olli; Niccolai, Elena; Amedei, Amedeo; Ivaldi, Federico; Clerico, Marinella; Contessa, Giulia; Uccelli, Antonio; Durelli, Luca; Novelli, Francesco

doi:10.4049/jimmunol.1004013

Cited by 28 publications

(25 citation statements)

References 24 publications

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“…The role of JAK2 in the modulation of IFN-γR2 was demonstrated as its transduction prevented rapid internalization and degradation of IFN-γR2 in JAK2-deficient γ2A cells. In others words, these data identify JAK2 as a critical factor that stabilizes IFN-γR2 surface expression in Th17 cells from patients with active MS, making them sensitive to IFN-γ [99]. …”

Section: Current and Future Clinical Applications Of Cytokine-medimentioning

confidence: 99%

RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

Amedei

Prisco

D’Elios

2012

IJMS

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Multiple sclerosis, the clinical features and pathological correlate for which were first described by Charcot, is a chronic neuroinflammatory disease with unknown etiology and variable clinical evolution. Although neuroinflammation is a descriptive denominator in multiple sclerosis based on histopathological observations, namely the penetration of leukocytes into the central nervous system, the clinical symptoms of relapses, remissions and progressive paralysis are the result of losses of myelin and neurons. In the absence of etiological factors as targets for prevention and therapy, the definition of molecular mechanisms that form the basis of inflammation, demyelination and toxicity for neurons have led to a number of treatments that slow down disease progression in specific patient cohorts, but that do not cure the disease. Current therapies are directed to block the immune processes, both innate and adaptive, that are associated with multiple sclerosis. In this review, we analyze the role of cytokines in the multiple sclerosis pathogenesis and current/future use of them in treatments of multiple sclerosis.

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Section: Current and Future Clinical Applications Of Cytokine-medimentioning

confidence: 99%

RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

Amedei

Prisco

D’Elios

2012

IJMS

Self Cite

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“…Cells were lysed with cell lysis buffer (0,5% NP-40, 150 mM NaCl, 50 mM Tris-HCl, 0,25 mM EDTA, 1 mM DTT, 1 mM Na 3 VO 4 and 1:2000 protease inhibitor cocktail (all from Sigma-Aldrich)) as in [46]. 40 μg total proteins were resolved by SDS-PAGE and electroblotted onto PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

L-Ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents

et al. 2016

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A growing body of evidence suggests that cancer stem cells (CSC) have the unique biological properties necessary for tumor maintenance and spreading, and function as a reservoir for the relapse and metastatic evolution of the disease by virtue of their resistance to radio- and chemo-therapies. Thus, the efficacy of a therapeutic approach relies on its ability to effectively target and deplete CSC. In this study, we show that CSC-enriched tumorspheres from breast cancer cell lines display an increased L-Ferritin uptake capability compared to their monolayer counterparts as a consequence of the upregulation of the L-Ferritin receptor SCARA5. L-Ferritin internalization was exploited for the simultaneous delivery of Curcumin, a natural therapeutic molecule endowed with antineoplastic action, and the MRI contrast agent Gd-HPDO3A, both entrapped in the L-Ferritin cavity. This theranostic system was able to impair viability and self-renewal of tumorspheres in vitro and to induce the regression of established tumors in mice. In conclusion, here we show that Curcumin-loaded L-Ferritin has a strong therapeutic potential due to the specific targeting of CSC and the improved Curcumin bioavailability, opening up the possibility of its use in a clinical setting.

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“…IFN-g signaling plays a key role in Th17 differentiation and function (27). It was already demonstrated that the neutralization of IFN-g effect by a specific mAb to IFN-g or to the IFN-gR1 chain was required for the massive development of activated T lymphocytes cultured in the presence of IL-23 into Th17 cells (28). The Hx-mediated control of CD4 + T cell responsiveness to IFN-g might be related to the Hx ability to modulate iron availability within cells (1), thus affecting the expression of Transferrin receptor that has already (12).…”

Section: The Journal Of Immunology 5455mentioning

confidence: 99%

Acute-Phase Protein Hemopexin Is a Negative Regulator of Th17 Response and Experimental Autoimmune Encephalomyelitis Development

Rolla

Ingoglia

Bardina

et al. 2013

The Journal of Immunology

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Hemopexin (Hx) is an acute-phase protein synthesized by hepatocytes in response to the proinflammatory cytokines IL-6, IL-1β, and TNF-α. Hx is the plasma protein with the highest binding affinity to heme and controls heme-iron availability in tissues and also in T lymphocytes, where it modulates their responsiveness to IFN-γ. Recent data have questioned regarding an anti-inflammatory role of Hx, a role that may be both heme-binding dependent and independent. The aim of this study was to investigate the role of Hx in the development of a T cell–mediated inflammatory autoimmune response. During experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis, Hx content in serum increased and remained high. When EAE was induced in Hx knockout (Hx−/−) mice, they developed a clinically earlier and exacerbated EAE compared with wild-type mice, associated to a higher amount of CD4+-infiltrating T cells. The severe EAE developed by Hx−/− mice could be ascribed to an enhanced expansion of Th17 cells accounting for both a higher disposition of naive T cells to differentiate toward the Th17 lineage and a higher production of Th17 differentiating cytokines IL-6 and IL-23 by APCs. When purified human Hx was injected in Hx−/− mice before EAE induction, Th17 expansion, as well as disease severity, were comparable with those of wild-type mice. Taken together, these data indicate that Hx has a negative regulatory role in Th17-mediated inflammation and prospect its pharmacological use to limit the expansion of this cell subset in inflammatory and autoimmune disease.

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Th17 Cells in Multiple Sclerosis Express Higher Levels of JAK2, Which Increases Their Surface Expression of IFN-γR2

Cited by 28 publications

References 24 publications

RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

RETRACTED: Multiple Sclerosis: The Role of Cytokines in Pathogenesis and in Therapies

L-Ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents

Acute-Phase Protein Hemopexin Is a Negative Regulator of Th17 Response and Experimental Autoimmune Encephalomyelitis Development

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