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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\u2013Cas9 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.<\/jats:p>","DOI":"10.4049\/jimmunol.2000719","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T21:01:30Z","timestamp":1618261290000},"page":"2029-2037","source":"Crossref","is-referenced-by-count":6,"title":["Conditional Deletions of <i>Hdc<\/i> Confirm Roles of Histamine in Anaphylaxis and Circadian Activity but Not in Autoimmune Encephalomyelitis"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8143-6644","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Morin","sequence":"first","affiliation":[{"name":"Neuroscience Unit, University Hospital Center of Quebec, Laval University , Quebec City, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-6786","authenticated-orcid":false,"given":"Noopur","family":"Singh","sequence":"additional","affiliation":[{"name":"Neuroscience Unit, University Hospital Center of Quebec, Laval University , Quebec City, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-8579","authenticated-orcid":false,"given":"Julius Baya","family":"Mdzomba","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, University Hospital Center of Quebec, Laval University , Quebec City, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5718-7206","authenticated-orcid":false,"given":"Aline","family":"Dumas","sequence":"additional","affiliation":[{"name":"Neuroscience Unit, University Hospital Center of Quebec, Laval University , Quebec City, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Patenaude","sequence":"additional","affiliation":[{"name":"Neuroscience Unit, University Hospital Center of Quebec, Laval University , Quebec City, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Pernet","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, University Hospital Center of Quebec, Laval University , Quebec City, Quebec ,","place":["Canada"]},{"name":"Department of Neurology, Inselspital Bern, University Hospital, University of Bern , Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0737-1539","authenticated-orcid":false,"given":"Luc","family":"Valli\u00e8res","sequence":"additional","affiliation":[{"name":"Neuroscience Unit, University Hospital Center of Quebec, Laval University , Quebec City, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"2025030417494500300_r1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/bies.20174","article-title":"Mammalian histidine decarboxylase: from structure to function","volume":"27","author":"Moya-Garcia","year":"2005","journal-title":"BioEssays"},{"key":"2025030417494500300_r2","first-page":"1","article-title":"Histamine in health and disease","volume":"17","author":"Repka-Ramirez","year":"2002","journal-title":"Clin. 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