TY - JOUR
T1 - A key regulatory role for histamine in experimental autoimmune encephalomyelitis
T2 - Disease exacerbation in histidine decarboxylase-deficient mice
AU - Musio, Silvia
AU - Gallo, Barbara
AU - Scabeni, Stefano
AU - Lapilla, Marilena
AU - Poliani, Pietro L.
AU - Matarese, Giuseppe
AU - Ohtsu, Hiroshi
AU - Galli, Stephen J.
AU - Mantegazza, Renato
AU - Steinman, Lawrence
AU - Pedotti, Rosetta
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=29644434680&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=29644434680&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.176.1.17
DO - 10.4049/jimmunol.176.1.17
M3 - Article
C2 - 16365391
AN - SCOPUS:29644434680
VL - 176
SP - 17
EP - 26
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -