Conditional Deletions of Hdc Confirm Roles of Histamine in Anaphylaxis and Circadian Activity but Not in Autoimmune Encephalomyelitis.
J Immunol
; 206(9): 2029-2037, 2021 05 01.
Article
em En
| MEDLINE
| ID: mdl-33846226
ABSTRACT
Histamine is best known for its role in allergies, but it could also be involved in autoimmune diseases such as multiple sclerosis. However, studies using experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis, have reported conflicting observations and suggest the implication of a nonclassical source of histamine. In this study, we demonstrate that neutrophils are the main producers of histamine in the spinal cord of EAE mice. To assess the role of histamine by taking into account its different cellular sources, we used CRISPR-Cas9 to generate conditional knockout mice for the histamine-synthesizing enzyme histidine decarboxylase. We found that ubiquitous and cell-specific deletions do not affect the course of EAE. However, neutrophil-specific deletion attenuates hypothermia caused by IgE-mediated anaphylaxis, whereas neuron-specific deletion reduces circadian activity. In summary, this study refutes the role of histamine in EAE, unveils a role for neutrophil-derived histamine in IgE-mediated anaphylaxis, and establishes a new mouse model to re-explore the inflammatory and neurologic roles of histamine.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Histamina
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Ritmo Circadiano
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Encefalomielite Autoimune Experimental
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Histidina Descarboxilase
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Anafilaxia
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá