Interferon-<i>γ</i>-modified dendritic cells suppress B cell function and ameliorate the development of experimental autoimmune myasthenia gravis

Adikari, S. B.; Lian, H.; Link, Hans; Huang, Yu‐Min; Xiao, Bao‐Guo

doi:10.1111/j.1365-2249.2004.02585.x

Cited by 40 publications

(28 citation statements)

References 27 publications

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“…In another experiment, pretreatment of splenic DCs from naive mice with IFN-␥ in vitro directly suppressed the Ag-presenting capacity of DCs (Fig. 6J), which was consistent with previous studies (42)(43)(44). Moreover, pretreatment of DCs with IFN-␥ attenuated eosinophilic inflammation induced by transfer of OVA-pulsed DCs and inhalation of OVA (Fig.…”

Section: In Vivo Ifn-␥ Gene Delivery Suppresses Overall DC Functions supporting

confidence: 89%

IFN-γ Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine

Nakagome

Okunishi

Imamura

et al. 2009

The Journal of Immunology

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Allergic inflammation in the airway is generally considered a Th2-type immune response. However, recent studies demonstrated that Th1- and Th17-type immune responses also play important roles in this process. IFN-γ is a Th1-type cytokine that generally counteracts the Th2 response. Although previous studies suggest that exogenous IFN-γ suppresses allergic airway inflammation, the mechanism of suppression has not been fully clarified. In this study, we elucidated whether IFN-γ suppresses Ag-induced immune responses including the production of Th1- and Th17-type cytokines in the lung, and examined its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IFN-γ-producing plasmid vector was delivered before systemic Ag sensitization. IFN-γ suppressed indicators of Th2-type immune responses such as airway eosinophilia, IL-5 and IL-13 production in the lung, and bronchial mucus production. Moreover, IFN-γ also suppressed the production of IL-17 and IFN-γ itself. The suppression was not mediated by inducing regulatory T cells or by inducing apoptosis in immunocytes. Instead, IFN-γ suppressed the Ag-presenting capacity and cytokine production of splenic dendritic cells and thus subsequently suppressed OVA-induced activation of CD4+ T cells. Furthermore, IFN-γ also attenuated allergic airway inflammation when delivered during the OVA challenge. Various functions of lung CD11c+ APCs and their migration to regional lymph nodes were also suppressed. These results suggest that the Th1 cytokine IFN-γ has broad immune regulatory potential through suppressing APC functions. They also suggest that delivery of IFN-γ could be an effective strategy for regulating Ag-induced immune responses in the lung.

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Section: In Vivo Ifn-␥ Gene Delivery Suppresses Overall DC Functions supporting

confidence: 89%

IFN-γ Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine

Nakagome

Okunishi

Imamura

et al. 2009

The Journal of Immunology

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“…The significance of this discrepancy becomes obvious when considering that MSCs pretreated by IFN-g became powerful inhibitors of activated B-cell growth. Interestingly, dendritic cells exposed to IFN-g before injection acquire therapeutic potential in an experimental autoimmune myasthenia gravis rat model, in association with an IDO-dependent inhibition of B-cell function in vivo (35).…”

Section: Discussionmentioning

confidence: 99%

Functional Alteration of the Lymphoma Stromal Cell Niche by the Cytokine Context: Role of Indoleamine-2,3 Dioxygenase

et al. 2009

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Human mesenchymal stem cells (MSC) strongly repress activated T-cell proliferation through the production of a complex set of soluble factors, including the tryptophancatabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which is induced by IFN-;. Conversely, MSCs support survival of follicular lymphoma (FL) B cells, in particular after exposure to tumor necrosis factor-A (TNF) and lymphotoxin-A1B2 (LT). The role of MSCs on normal and malignant B-cell growth in steady-state and inflammatory conditions remains to be fully explored. We show here that resting MSCs sustain activated normal B-cell proliferation and survival, whereas IFN-;-conditioned MSCs mediate IDOdependent B-cell growth arrest and apoptosis. IFN-;, TNF, and LT are significantly overexpressed by the microenvironment of invaded FL-lymph nodes, but their relative expression patterns are highly heterogeneous between samples. In vitro, IFN-; abrogates the B-cell supportive phenotype induced by TNF and LT on MSCs. Moreover, IFN-; overrules the growth promoting effect of MSCs on primary purified FL B cells. Altogether, these results underline the crucial role of the cytokine context in the local crosstalk between malignant cells and their microenvironment and provide new insights into our knowledge of the FL cell niche that emerges as a new promising target for innovative therapeutic strategies. [Cancer Res 2009;69(7):3228-37]

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“…Earlier studies showed that in rats, presentation of AChR epitopes by unsuitable APCs (fixed B cells that had been incubated with AChR under conditions favoring AChR uptake and processing) caused unresponsiveness of the AChR-specific CD4 + T cells to further stimulation with AChR (113). More recently, several studies have demonstrated that DCs, especially after treatment with TGF-β, IFN-γ, or IL-10, when injected into rats with developing or ongoing EAMG, suppressed or ameliorated the myasthenic symptoms (114)(115)(116). The effect was correlated with a reduced production of anti-AChR Abs without a reduced proliferative response of T cells to the AChR.…”

Section: The Futurementioning

confidence: 99%

Myasthenia gravis: past, present, and future

Conti‐Fine

Milani²,

Kaminski³

2006

J. Clin. Invest.

560

512

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Pathogenesis of MG: current state of the artStructure and function of the NMJ. The terminal arborization of α-motor neuron axons from the ventral horns of the spinal cord and brainstem provides the nerve terminals that form the NMJ (Figure 1). These myelinated axons reach the muscles through peripheral nerves; then each axon divides into branches that innervate many individual muscle fibers. As it approaches its target fiber, each branch loses the myelin sheath and further subdivides into many presynaptic boutons, which contain ACh-loaded synaptic vesicles and face the surface of the muscle fiber at the NMJ ( Figure 1). The synaptic bouton and the muscle surface are separated by the synaptic cleft, a 20 nm-thick space that contains acetylcholinesterase (AChE) and other proteins and proteoglycans involved in

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Interferon-γ-modified dendritic cells suppress B cell function and ameliorate the development of experimental autoimmune myasthenia gravis

Cited by 40 publications

References 27 publications

IFN-γ Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine

IFN-γ Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine

Functional Alteration of the Lymphoma Stromal Cell Niche by the Cytokine Context: Role of Indoleamine-2,3 Dioxygenase

Myasthenia gravis: past, present, and future

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