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Journal article
Autoimmune disease-associated histamine receptor H1 alleles exhibit differential protein trafficking and cell surface expression
The Journal of immunology (1950), v 180(11), pp 7471-7479
01 Jun 2008
PMID: 18490747
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Structural polymorphisms (L263P, M313V, and S331P) in the third intracellular loop of the murine histamine receptor H(1) (H(1)R) are candidates for Bphs, a shared autoimmune disease locus in experimental allergic encephalomyelitis and experimental allergic orchitis. The P-V-P haplotype is associated with increased disease susceptibility (H(1)R(S)) whereas the L-M-S haplotype is associated with less severe disease (H(1)R(R)). In this study, we show that selective re-expression of the H(1)R(S) allele in T cells fully complements experimental allergic encephalomyelitis susceptibility and the production of disease-associated cytokines while selective re-expression of the H(1)R(R) allele does not. Mechanistically, we show that the two H(1)R alleles exhibit differential cell surface expression and altered intracellular trafficking, with the H(1)R(R) allele being retained within the endoplasmic reticulum. Moreover, we show that all three residues (L-M-S) comprising the H(1)R(R) haplotype are required for altered expression. These data are the first to demonstrate that structural polymorphisms influencing cell surface expression of a G protein-coupled receptor in T cells regulates immune functions and autoimmune disease susceptibility.
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Details
- Title
- Autoimmune disease-associated histamine receptor H1 alleles exhibit differential protein trafficking and cell surface expression
- Creators
- Rajkumar Noubade - Department of Medicine, University of Vermont, Burlington, VT 05405, USANaresha SaligramaKaren SpachRoxana Del RioElizabeth P BlankenhornTheodoros KantidakisGraeme MilliganMercedes RinconCory Teuscher
- Publication Details
- The Journal of immunology (1950), v 180(11), pp 7471-7479
- Publisher
- American Association of Immunologists (AAI); United States
- Grant note
- NS036526 / NINDS NIH HHS R01 NS036526 / NINDS NIH HHS AI058052 / NIAID NIH HHS R01 NS036526-09A1 / NINDS NIH HHS R01 AI058052-05 / NIAID NIH HHS R01 AI058052 / NIAID NIH HHS R01 AI051454-05 / NIAID NIH HHS R01 AI041747 / NIAID NIH HHS AI045666 / NIAID NIH HHS P01 AI045666-050004 / NIAID NIH HHS R01 NS036526-10 / NINDS NIH HHS R01 NS069628 / NINDS NIH HHS R56 AI051454 / NIAID NIH HHS R01 AI058052-04 / NIAID NIH HHS R01 AI051454 / NIAID NIH HHS R01 NS036526-11 / NINDS NIH HHS P20 RR021905 / NCRR NIH HHS R01 AI041747-09 / NIAID NIH HHS AI051454 / NIAID NIH HHS AI041747 / NIAID NIH HHS R21 AI051454 / NIAID NIH HHS R01 AI041747-10 / NIAID NIH HHS P01 AI045666 / NIAID NIH HHS R01 AI051454-04 / NIAID NIH HHS R01 NS036526-12 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000257507300044
- Scopus ID
- 2-s2.0-47249134977
- Other Identifier
- 991014878468104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology