ArticleThe American journal of pathology2004
Attenuation of Th1 effector cell responses and susceptibility to experimental allergic encephalomyelitis in histamine H2 receptor knockout mice is due to dysregulation of cytokine production by antigen-presenting cells.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
- The sleep-wake cycle: molecular mechanisms, disorders, and therapeutic targets in the context of energy metabolism.Signal transduction and targeted therapy · 2026Review
- Disturbances of Ruminal Microbiota and Liver Inflammation, Mediated by LPS and Histamine, in Dairy Cows Fed a High-Concentrate Diet.Animals : an open access journal from MDPI · 2024Article
- Phenotypic and genomic characterisation of performance of tropically adapted chickens raised in smallholder farm conditions in Ethiopia.Frontiers in genetics · 2024Article
- Seasonal Changes in Serum Metabolites in Multiple Sclerosis Relapse.International journal of molecular sciences · 2023Article
- Histamine: A Mediator of Intestinal Disorders-A Review.Metabolites · 2022Review
- The Histamine and Multiple Sclerosis Alliance: Pleiotropic Actions and Functional Validation.Current topics in behavioral neurosciences · 2022Article
- Food Intolerance: The Role of Histamine.Nutrients · 2021Review
- Expression of Histidine Decarboxylase and Its Roles in Inflammation.International journal of molecular sciences · 2019Review
- Type 2 Inflammatory Responses in Autoimmune Demyelination of the Central Nervous System: Recent Advances.Journal of immunology research · 2019Review
- Histamine activates inflammatory response and depresses casein synthesis in mammary gland of dairy cows during SARA.BMC veterinary research · 2018Article
- The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets.Frontiers in immunology · 2018Review
- Pharmacological targeting of allergen-specific T lymphocytes.Immunology letters · 2017Review
- International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.Pharmacological reviews · 2015Review
- Histamine promotes the development of monocyte-derived dendritic cells and reduces tumor growth by targeting the myeloid NADPH oxidase.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring.Genome biology · 2015Article
- Histamine H₂ receptor signaling × environment interactions determine susceptibility to experimental allergic encephalomyelitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Systemic lack of canonical histamine receptor signaling results in increased resistance to autoimmune encephalomyelitis.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- The histaminergic network in the brain: basic organization and role in disease.Nature reviews. Neuroscience · 2013Review
- Neuroendocrine immunoregulation in multiple sclerosis.Clinical & developmental immunology · 2013Review
- Combinatorial roles for histamine H1-H2 and H3-H4 receptors in autoimmune inflammatory disease of the central nervous system.European journal of immunology · 2012Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Histamine, a biogenic amine with both neurotransmitter and vasoactive properties, is well recognized as an immunomodulatory agent in allergic and inflammatory reactions. It also plays a regulatory role in the development of antigen-specific immune responses. CD4+ T-cells from histamine H1 receptor (H1R)-deficient (H1RKO) mice produce significantly less interferon-gamma and more interleukin (IL)-4 in in vitro recall assays compared to wild-type controls. H1RKO mice are also less susceptible to acute early-phase experimental allergic encephalomyelitis indicating that H1R signaling in CD4+ T cells plays a central role in regulating pathogenic T-cell responses. In this study, we show that mice lacking histamine H2 receptor (H2RKO) are similar to H1RKO mice in that they develop encephalitogen-specific T-cell responses as assessed by proliferation and IL-2 production and present with less severe acute early-phase experimental allergic encephalomyelitis. However, unlike T cells from H1RKO mice, which exhibit a strong Th2 bias, T cells from H2RKO mice do not. Rather, they are uniquely characterized by a significant inhibition of Th1 effector cell responses. Given that both histamine and adjuvants such as pertussis toxin modulate antigen-presenting cell (APC) maturation and function, including T-cell-polarizing activity, we analyzed the cytokines/chemokines secreted by APCs from wild-type, H1RKO, and H2RKO mice. Significant differences in cytokine/chemokine production by APCs from unimmunized and immunized mice were delineated. APCs from H2RKO mice produce significantly less IL-12 and IL-6 and markedly greater amounts of MCP-1 compared to wild-type and H1RKO mice. Because MCP-1 is known to inhibit IL-12 production, the failure of H2RKO mice to generate encephalitogenic Th1 effector cell responses is consistent with inhibition of negative regulation of MCP-1 secretion by H2R signaling in APCs.
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