DAP12 is required for macrophage recruitment to the lung in response to cigarette smoke and chemotaxis toward CCL2.

DAP12 is an adapter protein that associates with several receptors in macrophages. Little is known about the biological role of DAP12 in alveolar macrophages. In genome-wide profiling, we previously found that two DAP12-associated receptors, myeloid DAP12-associated lectin-1 and triggering receptor expressed on myeloid cells 2 (TREM2), were highly induced in alveolar macrophages from habitual smokers.

T-helper type 2-driven inflammation defines major subphenotypes of asthma.

Rationale: T-helper type 2 (Th2) inflammation, mediated by IL-4, IL-5, and IL-13, is considered the central molecular mechanism underlying asthma, and Th2 cytokines are emerging therapeutic targets. However, clinical studies increasingly suggest that asthma is heterogeneous.

Objectives: To determine whether this clinical heterogeneity reflects heterogeneity in underlying molecular mechanisms related to Th2 inflammation.

Alveolar macrophage recruitment and activation by chronic second hand smoke exposure in mice.

Approximately 15% of cases of COPD occur in non-smokers. Among the potential risk factors for COPD in non-smokers is second-hand smoke (SHS) exposure. However, the Surgeon General reported in 2006 that the evidence linking second hand smoke and COPD is insufficient to infer a causal relationship, largely because current evidence does not establish a biological link.

Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids.

Airway inflammation and epithelial remodeling are two key features of asthma. IL-13 and other cytokines produced during T helper type 2 cell-driven allergic inflammation contribute to airway epithelial goblet cell metaplasia and may alter epithelial-mesenchymal signaling, leading to increased subepithelial fibrosis or hyperplasia of smooth muscle. The beneficial effects of corticosteroids in asthma could relate to their ability to directly or indirectly decrease epithelial cell activation by inflammatory cells and cytokines.