Publications

Type 2 inflammation unfolds over time and is coordinated by remarkably durable CD4+ Th2 cell responses, standing in contrast to the collapse of adaptive immunity seen in chronic infection and malignancy. In experimental models, short-lived Th2 effector cells and type 2 innate lymphocytes (ILC2) contribute to acute type 2 inflammation, yet the cellular architecture that […]

Platelets amplify type 2 inflammation (T2I) through incompletely understood mechanisms. Depletion of platelets markedly attenuated mast cell (MC) activation in a model of aspirin exacerbated respiratory disease (AERD) that depends on IL-33 and cysteinyl leukotrienes (cysLTs). We demonstrate an IL-33-driven feed-forward loop between platelets and MCs. IL-33 neutralization prevented increases in cysLTs and CXCL7, a […]

Determining spatial location of cells within tissues gives vital insight into the interactions between resident and inflammatory cells and is a critical factor for uncoupling the mechanisms driving disease. Here, we apply single-cell spatial transcriptomics to reveal the airway wall landscape in health and during asthma. We identified proinflammatory cellular ecosystems that exist within discrete […]

Studies using mouse models of airway disease have advanced our understanding of the mechanisms driving eosinophilic airway inflammation and demonstrated potential therapeutic targets in asthma.

Over the past 2 decades, mechanistic studies of allergic and type 2 (T2)-mediated airway inflammation have led to multiple approved therapies for the treatment of moderate-to-severe asthma. The approval and availability of these monoclonal antibodies targeting IgE, a T2 cytokine (IL-5) and/or cytokine receptors (IL-5Rα, IL-4Rα) has been central to the progresses made in the […]

Mast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MCTs are phenotypically distinct from subepithelial MCs (MCTCs), signals driving human MCT differentiation and this subset's contribution to inflammation remain unexplored. Here, we have identified TGF-β as a key driver of […]

The cysteinyl leukotrienes (CysLTs), LTC(4), LTD(4), and LTE(4), are potent lipid mediators derived from arachidonic acid through the 5-lipoxygenase pathway. These mediators produce both inflammation and bronchoconstriction through three distinct G protein-coupled receptors (GPCRs)-CysLT(1), CysLT(2), and OXGR1 (also known as CysLT(3) or GPR99). While CysLT-mediated functions in the effector phase of allergic inflammation and asthma […]

Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells […]

Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)-33 signaling through its membrane-bound receptor, ST2. Soluble (s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E(2) (PGE(2)) drives production of sST2 to limit features of lung T2I. PGE(2)-deficient mice […]

CONCLUSION: In addition to type 2 inflammation, innate and IL-6-related cytokines are also elevated in the respiratory tract in AERD. Both OSM and IL-6 are locally produced in nasal polyps and likely promote pathology by negatively affecting epithelial barrier function. IL-4Rα blockade, although seemingly directed at type 2 inflammation, also decreases mediators of innate inflammation […]