CCR8 positive T cells and chronic allergic inflammation in asthma

Massachusetts General Hospital, Boston MA

Investigators

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Abstract

DESCRIPTION (provided by applicant): 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.