- Director, CIHR National Training Program in Allergy and Asthma
- Canada Research Chair in Immune Regulation
- Professor, Department of Immunology
- Professor, Medical Microbiology
- Professor, Pediatrics and Child Health
Post Doctoral Fellowship, Harvard Medical School (1983-1986)
Ph.D. (Immunology), University of Western Ontario (1983)
B.Sc. (Hons), Queen's University, Kingston (1978)
Department of Immunology
University of Manitoba
Faculty of Medicine
427 Apotex Centre
750 McDermot Avenue
Phone: (204) 789-3793
Fax: (204) 789-3921
Lab: (204) 789-3740
Chemokines in immune regulation of human allergic disease
Much attention centers on the contributions of Th1 vs Th2 biased cytokine production
in respiratory hypersensitivity. Chemokines are a subfamily of cytokines with
pivotal roles in leukocyte trafficking and ontogeny. We recently discovered
important roles for CXCR-3 binding chemokines in modulating ongoing allergen
specific immunity, reinforcing the proclivity of healthy, non-atopic
humans towards protective (rather than Th2 dominated) immune responses to allergen.
Here, we propose to focus on the chemokine responses which are disregulated
in allergic respiratory tract disease and identify those associated with protective
immunity that is thought to underlie clinical tolerance in non-atopic controls.
The regulatory mechanisms that control differential expression of Th1 vs. Th2
biased chemokine production in individuals with ongoing immediate hypersensitivity
vs. those with clinical tolerance to the same seasonal environmental allergens
will be determined as will the role played by differential chemokine reception
expression and in vivo modulation in response to seasonal environmental Ag exposure.
Global hypothesis: Altered allergen-specific chemokine
production, and chemokine receptor expression, are hallmarks of human
allergic respiratory tract disease that are tightly integrated with the
Th1/Th2 balance seen upon allergen re-exposure in those exhibiting clinical
tolerance vs. hypersensitivity.
Allergic and healthy individuals exhibit differential allergen-specific
chemokine production and responsiveness among immune cells.
Utilizing the following,
- 40 healthy participants (control)
- 40 allergic participants with mild allergic rhinitis during the
grass pollen season but no evidence of asthma
- 40 allergic participants with mild intermittent asthma AND mild
allergic rhinitis during the grass pollen season, we will:
In summary, this study capitalizes on our recent discoveries of novel
immunomodulatory properties of chemokines and will provide an integrated
view of the roles played by characteristic Th1 (CXCR3) and Th2 (CCR4)
immunity associated families in influencing maintenance of ongoing respiratory
allergic disease vs. clinical tolerance.
- Determine cross sectionally and longitudinally, the extent to which
differential chemokine production in the CXCR3 and CCR4 families is a
hallmark of atopic vs. healthy controls restricted to the allergen-specific
component of the immune response. Using short term primary culture systems,
immunocytochemistry, and sensitive ELISAs for allergen-driven chemokine
protein expression that we developed, we will investigate the in vivo
regulation of CXCR3 and CCR4 chemokine families. We will identify differences
in chemokine expression and the mechanisms controlling their regulation,
the impact of natural in vivo allergen re-exposure, determine the extent
to which these are restricted to the allergen-specific component of the
response and investigate the relationship between Ag-driven cytokine synthesis
and chemokine production in populations with well established hypersensitivity
vs. clinical tolerance.
- Determine the functional significance of differential CD4T cell chemokine
and receptor expression or function in recall responses and identify the
mechanisms underlying this difference. Pursuing the striking capacity
that we discovered of CXCR3 ligands to selectively enhance protective
recall responses of healthy individuals to environmental allergens and
our very recent finding of the hypo-responsiveness of allergics to this
pathway, we will investigate the mechanisms through which protective vs.
Th2 biased immune responses to allergens impact on maintenance of ongoing
clinical tolerance vs. hypersensitivity.
For more on Dr. HayGlass's research interests, see:
Latest revision: February 2, 2009