Sarcoidosis is a systemic granulomatous disease that prominently affects the lungs in almost all cases. There are multiple studies suggesting an interesting functional role of dendritic cells in this disease, which – together with the fact that our medical center is a longstanding center of excellence in sarcoidosis research and a regional referral center for patients with the whole spectrum of clinical disease phenotypes - makes it a prime candidate to assess the different DC subpopulations in affected human lung and locoregionary lymph node tissue and to correlate the findings with the various different disease phenotypes we see at Mount Sinai (resolving disease vs. chronically progressive or fibrosing disease).

Idiopathic pulmonary fibrosis (IPF) is a chronically progressive, irreversible and ultimately fatal fibrosing lung disease. The disease affects many patients worldwide without any geographical or racial predilection. The prevalence in the US is estimated at around 20 cases per 100,000 for males and 13 cases per 100,000 for females. The disease imposes both a high symptom burden and an ultimately fatal prognosis on affected patients and their families. The median survival time after diagnosis currently is only 2.5 to 3.5 years. Our understanding of this disease, its cause(s) and underlying pathogenetic mechanisms is poor. There is no effective treatment available to date. Secondary forms of pulmonary fibrosis affect a much higher number of patients, but exact numbers on prevalence, morbidity and mortality are difficult to estimate given the heterogeneity of the different underlying conditions. A characterization of how the different dendritic cell subsets are dysfunctional in pulmonary fibrosis will help to better understand the underlying pathogenetic mechanisms and may offer new insights into therapeutic options to halt the progression of the fibrotic remodeling process in patients afflicted with this condition.

The respiratory tract is one of the organ systems in the human body directly confronted with the outside world, making effective immune surveillance and defense mechanisms essential. Dendritic cells (DCs) are emerging as prominent regulators of immune responses in the lung. Historically, a large body of work has looked into the anatomic and functional properties of DCs in the respiratory system. Recent studies utilizing novel research techniques are rapidly expanding our knowledge. Most of this recent work has been done using animal models. We are characterizing the phenotypes of dendritic cells in the normal human lung and in disease states in which dendritic cells are either proven or implicated to play important roles in pathogenesis and pathophysiology, namely, but not limited to, sarcoidosis and idiopathic as well as secondary forms of pulmonary fibrosis.