A Key Regulatory Role for Histamine in Experimental Autoimmune Encephalomyelitis: Disease Exacerbation in Histidine Decarboxylase-Deficient Mice

Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediat...

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Veröffentlicht in:Journal of Immunology 2006-01, Vol.176 (1), p.17-26
Hauptverfasser: Musio, Silvia, Gallo, Barbara, Scabeni, Stefano, Lapilla, Marilena, Poliani, Pietro L, Matarese, Giuseppe, Ohtsu, Hiroshi, Galli, Stephen J, Mantegazza, Renato, Steinman, Lawrence, Pedotti, Rosetta
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container_issue 1
container_start_page 17
container_title Journal of Immunology
container_volume 176
creator Musio, Silvia
Gallo, Barbara
Scabeni, Stefano
Lapilla, Marilena
Poliani, Pietro L
Matarese, Giuseppe
Ohtsu, Hiroshi
Galli, Stephen J
Mantegazza, Renato
Steinman, Lawrence
Pedotti, Rosetta
description Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediated disease with similarities to human multiple sclerosis. To study the comprehensive contribution of endogenous histamine to the expression of EAE, we attempted to induce EAE in histidine decarboxylase-deficient mice, which are genetically unable to make histamine. In this study, we show that EAE is significantly more severe in HDC-/-, histamine-deficient mice, with diffuse inflammatory infiltrates, including a prevalent granulocytic component, in the brain and cerebellum. Unlike splenocytes from wild-type mice, splenocytes from HDC-/- mice do not produce histamine in response to the myelin Ag, whereas production of IFN-gamma, TNF, and leptin are increased in HDC-/- splenocytes in comparison to those from wild-type mice. Endogenous histamine thus appears to regulate importantly the autoimmune response against myelin and the expression of EAE, in this model, and to limit immune damage to the CNS. Understanding which receptor(s) for histamine is/are involved in regulating autoimmunity against the CNS might help in the development of new strategies of treatment for EAE and multiple sclerosis.
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subjects Animals
Brain - immunology
Brain - pathology
Chemokine CCL2 - biosynthesis
Encephalomyelitis, Autoimmune, Experimental - immunology
Glycoproteins - immunology
Histamine
Histidine Decarboxylase - deficiency
Interferon-gamma - biosynthesis
Leptin - biosynthesis
Mice
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments - immunology
T-Lymphocytes - immunology
Tumor Necrosis Factor-alpha - biosynthesis
title A Key Regulatory Role for Histamine in Experimental Autoimmune Encephalomyelitis: Disease Exacerbation in Histidine Decarboxylase-Deficient Mice
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