Allergic diseases, especially asthma, are highly prevalent within the United States and the developed world and cause significant morbidity in affected patients. However, the factors that mediate severe and chronic allergic inflammation remain incompletely elucidated. Recent studies from our laboratory and others indicate that CCR8 and its ligands (including newly described CCR8 ligands: murine CCL8 and human CCL18) may play a key role in severe and chronic allergic inflammation. We hypothesize that CCR8 expression is enriched on allergen-specific CD4+ T cells during severe or chronic allergic inflammation and that CCR8 and its ligands represent a key chemokine receptor-ligand axis that drives eosinophilic inflammation in human asthma.
We aim to generate a CCR8 reporter mouse to identify and track CCR8-expressing cells. Using this model, we will help elucidate the role of CCR8 expression on allergen-specific Th2 cells and other immune cells in chronic allergic inflammation in a mouse model of asthma. Furthermore, we will extend these findings to humans by investigating the role of CCR8 in allergen-specific CD4+ Th2 cell-mediated airway inflammation in human asthma.

Public Health Relevance

This project addresses mechanisms that drive chronic allergic inflammation. There has been controversy regarding CCR8 and its role in allergic inflammation, and our lab has recently discovered two new mammalian CCR8 ligands, CCL8 in mice, and CCL18 in humans, whose roles in allergic inflammation have yet to be fully clarified. Our proposed studies will help elucidate the mechanisms that underlie chronic allergic inflammation with regard to CCR8 and its ligands in mice and in humans.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI108125-01A1
Application #
8718084
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Prograis, Lawrence J
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199