A key regulatory role for histamine in experimental autoimmune encephalomyelitis: Disease exacerbation in histidine decarboxylase-deficient mice

Silvia Musio, Barbara Gallo, Stefano Scabeni, Marilena Lapilla, Pietro L. Poliani, Giuseppe Matarese, Hiroshi Ohtsu, Stephen J. Galli, Renato Mantegazza, Lawrence Steinman, Rosetta Pedotti

Research output: Contribution to journalArticle

Abstract

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-γ, 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.

Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalJournal of Immunology
Volume176
Issue number1
Publication statusPublished - Jan 1 2006

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Histidine Decarboxylase
Autoimmune Experimental Encephalomyelitis
Histamine
Autoimmune Diseases
Disease Progression
Histamine Receptors
Myelin Sheath
Autoimmunity
Multiple Sclerosis
Th1-Th2 Balance
Immunoglobulin Class Switching
Leptin
Cerebellum
Pharmacology
Cytokines
Brain

ASJC Scopus subject areas

  • Immunology

Cite this

Musio, S., Gallo, B., Scabeni, S., Lapilla, M., Poliani, P. L., Matarese, G., ... Pedotti, R. (2006). A key regulatory role for histamine in experimental autoimmune encephalomyelitis: Disease exacerbation in histidine decarboxylase-deficient mice. Journal of Immunology, 176(1), 17-26.

A key regulatory role for histamine in experimental autoimmune encephalomyelitis : Disease exacerbation in histidine decarboxylase-deficient mice. / Musio, Silvia; Gallo, Barbara; Scabeni, Stefano; Lapilla, Marilena; Poliani, Pietro L.; Matarese, Giuseppe; Ohtsu, Hiroshi; Galli, Stephen J.; Mantegazza, Renato; Steinman, Lawrence; Pedotti, Rosetta.

In: Journal of Immunology, Vol. 176, No. 1, 01.01.2006, p. 17-26.

Research output: Contribution to journalArticle

Musio, S, Gallo, B, Scabeni, S, Lapilla, M, Poliani, PL, Matarese, G, Ohtsu, H, Galli, SJ, Mantegazza, R, Steinman, L & Pedotti, R 2006, 'A key regulatory role for histamine in experimental autoimmune encephalomyelitis: Disease exacerbation in histidine decarboxylase-deficient mice', Journal of Immunology, vol. 176, no. 1, pp. 17-26.
Musio, Silvia ; Gallo, Barbara ; Scabeni, Stefano ; Lapilla, Marilena ; Poliani, Pietro L. ; Matarese, Giuseppe ; Ohtsu, Hiroshi ; Galli, Stephen J. ; Mantegazza, Renato ; Steinman, Lawrence ; Pedotti, Rosetta. / A key regulatory role for histamine in experimental autoimmune encephalomyelitis : Disease exacerbation in histidine decarboxylase-deficient mice. In: Journal of Immunology. 2006 ; Vol. 176, No. 1. pp. 17-26.
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