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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
A single nucleotide polymorphism in Tyk2 controls susceptibility to experimental allergic encephalomyelitis
Karen M Spach1, Rajkumar Noubade, Ben McElvany
1Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 5, 2009
Summary
Tyrosine kinase-2 (Tyk2) gene mutations influence autoimmune disease susceptibility. Environmental factors can modify this genetic contribution, highlighting gene-environment interactions in autoimmune conditions.
Area of Science:
- Immunology
- Genetics
- Autoimmune Diseases
Background:
- Genetic factors influence susceptibility to immunopathologic and autoimmune diseases.
- B10.D1-H2(q)/SgJ mice with a tyrosine kinase-2 (Tyk2) gene mutation are susceptible to Toxoplasma gondii but resistant to autoimmune arthritis.
- Wild-type B10.Q/Ai mice are susceptible to autoimmune arthritis.
Purpose of the Study:
- To investigate the role of Tyk2 in experimental allergic encephalomyelitis (EAE), a model for autoimmune disease.
- To determine if Tyk2 is a shared susceptibility gene across different autoimmune models.
- To explore the impact of environmental factors on Tyk2-mediated autoimmune disease susceptibility.
Main Methods:
- Experimental allergic encephalomyelitis (EAE) was induced in B10.D1-H2(q)/SgJ (Tyk2(A)) and B10.Q/Ai (Tyk2(G)) mice using myelin oligodendrocyte glycoprotein peptide 79-96.
- The effect of pertussis toxin (PTX) on EAE resistance in B10.D1-H2(q)/SgJ mice was assessed.
- Cytokine and chemokine levels were measured in response to PTX treatment.
Main Results:
- B10.D1-H2(q)/SgJ mice (Tyk2(A)) were resistant to EAE, while B10.Q/Ai mice (Tyk2(G)) were susceptible.
- A single Tyk2(G) allele conferred EAE susceptibility in F(1) hybrids.
- Pertussis toxin (PTX) treatment overrode EAE resistance in B10.D1-H2(q)/SgJ mice, increasing numerous cytokines and chemokines, notably RANTES, IL-6, and IFN-gamma.
- Tyk2 is identified as a shared autoimmune disease susceptibility gene.
Conclusions:
- Tyk2 plays a significant role in autoimmune disease susceptibility.
- Genetic susceptibility conferred by Tyk2 can be modulated by environmental factors, such as those mimicking infectious agents.
- Gene-by-environment interactions are crucial in understanding autoimmune disease development.
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