Journal article
A Single Nucleotide Polymorphism in Tyk2 Controls Susceptibility to Experimental Allergic Encephalomyelitis
The Journal of immunology (1950), v 182(12), pp 7776-7783
15 Jun 2009
PMID: 19494301
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Genes controlling immunopathologic diseases of differing etiopathology may also influence susceptibility to autoimmune disease. B10.D1-
H2
q
/SgJ mice with a 2538 G→A missense mutation in
tyrosine kinase-2
(
Tyk2
) are susceptible to
Toxoplasma gondii
, yet resistant to autoimmune arthritis, unlike the wild-type B10.Q/Ai substrain. To understand if
Tyk2
is also important in a second autoimmune model, experimental allergic encephalomyelitis (EAE) was induced in B10.D1-
H2
q
/SgJ (
Tyk2
A
) and B10.Q/Ai (
Tyk2
G
) mice with myelin oligodendrocyte glycoprotein peptide
79–96
. B10.D1-
H2
q
/SgJ (
Tyk2
A
) mice were resistant to EAE while B10.Q/Ai (
Tyk2
G
) mice were susceptible and a single copy of the
Tyk2
G
allele conferred EAE susceptibility in F
1
hybrids. Furthermore, EAE susceptibility in B10.D1-
H2
q
/SgJ (
Tyk2
A
) mice was complemented when pertussis toxin (PTX) was used to mimic the effects of environmental factors derived from infectious agents. Numerous cytokines and chemokines were increased when PTX was included in the immunization protocol. However, only RANTES, interleukin-6, and interferon-γ increased significantly with both genetic compensation and PTX complementation. These data indicate that
Tyk2
is a shared autoimmune disease susceptibility gene that can be complemented both genetically and environmentally. Single nucleotide polymorphisms like the one that distinguishes
Tyk2
alleles are of considerable significance given the potential role of gene-by-environment interactions in autoimmune disease susceptibility.
Metrics
Details
- Title
- A Single Nucleotide Polymorphism in Tyk2 Controls Susceptibility to Experimental Allergic Encephalomyelitis
- Creators
- Karen M Spach - Department of Medicine, University of Vermont, Burlington, VT, USA 05405Rajkumar Noubade - Department of Medicine, University of Vermont, Burlington, VT, USA 05405Ben McElvany - Department of Medicine, University of Vermont, Burlington, VT, USA 05405William F Hickey - Department of Pathology, Dartmouth Medical School, Hanover, NH, USA, 03755Elizabeth P Blankenhorn - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA 19129Cory Teuscher - Department of Medicine, University of Vermont, Burlington, VT, USA 05405
- Publication Details
- The Journal of immunology (1950), v 182(12), pp 7776-7783
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000266833900048
- Scopus ID
- 2-s2.0-67649198508
- Other Identifier
- 991014878027704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology