Journal article
Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility
PloS one, v 8(7), pe62743
22 Jul 2013
PMID: 23894272
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Histamine H
3
receptor (
Hrh3
/H
3
R) is primarily expressed by neurons in the central nervous system (CNS) where it functions as a presynaptic inhibitory autoreceptor and heteroreceptor. Previously, we identified an H
3
R-mediated central component in susceptibility to experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis (MS), related to neurogenic control of blood brain barrier permeability and peripheral T cell effector responses. Furthermore, we identified
Hrh3
as a positional candidate for the EAE susceptibility locus
Eae8
. Here, we characterize
Hrh3
polymorphisms between EAE-susceptible and resistant SJL and B10.S mice, respectively, and show that
Hrh3
isoform expression in the CNS is differentially regulated by acute peripheral inflammatory stimuli in an allele-specific fashion. Next, we show that
Hrh3
is not expressed in any subpopulations of the immune compartment, and that secondary lymphoid tissue is anatomically poised to be regulated by central H
3
R signaling. Accordingly, using transcriptome analysis, we show that, inflammatory stimuli elicit unique transcriptional profiles in the lymph nodes of H
3
RKO mice compared to WT mice, which is indicative of negative regulation of peripheral immune responses by central H
3
R signaling. These results further support a functional link between the neurogenic control of T cell responses and susceptibility to CNS autoimmune disease coincident with acute and/or chronic peripheral inflammation. Pharmacological targeting of H
3
R may therefore be useful in preventing the development and formation of new lesions in MS, thereby limiting disease progression.
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Details
- Title
- Histamine H3 Receptor Integrates Peripheral Inflammatory Signals in the Neurogenic Control of Immune Responses and Autoimmune Disease Susceptibility
- Creators
- Dimitry N KrementsovEmma H WallRebecca A MartinMeenakumari SubramanianRajkumar NoubadeRoxana Del RioGary M MaweJeffrey P BondMatthew E PoynterElizabeth P BlankenhornCory Teuscher
- Publication Details
- PloS one, v 8(7), pe62743
- Publisher
- Public Library of Science; San Francisco, USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000322132100001
- Scopus ID
- 2-s2.0-84880681099
- Other Identifier
- 991014877875904721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology