Abstract
Idiopathic pulmonary fibrosis (IPF) is the most devastating progressive interstitial lung disease that remains refractory to treatment. Pathogenesis of IPF relies on the aberrant cross-talk between injured alveolar cells and myofibroblasts, which ultimately leads to an aberrant fibrous reaction. The contribution of the immune system to IPF remains not fully explored. Recent evidence suggests that both innate and adaptive immune responses may participate in the fibrotic process. Dendritic cells (DCs) are the most potent professional antigen-presenting cells that bridge innate and adaptive immunity. Also, they exert a crucial role in the immune surveillance of the lung, where they are strategically placed in the airway epithelium and interstitium. Immature DCs accumulate in the IPF lung close to areas of epithelial hyperplasia and fibrosis. Conversely, mature DCs are concentrated in well-organized lymphoid follicles along with T and B cells and bronchoalveolar lavage of IPF patients. We have recently shown that all sub-types of peripheral blood DCs (including conventional and plasmacytoid DCs) are severely depleted in therapy naïve IPF patients. Also, the low frequency of conventional CD1c+ DCs is predictive of a worse prognosis. The purpose of this mini-review is to focus on the main evidence on DC involvement in IPF pathogenesis. Unanswered questions and opportunities for future research ranging from a better understanding of their contribution to diagnosis and prognosis to personalized DC-based therapies will be explored.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating fatal lung disease that usually remains refractory to treatment [1,2,3], with an estimated median survival of 2 to 5 years from the first diagnosis
common DC progenitors (CDPs) are restricted to the bone marrow, where they give rise to plasmacytoid dendritic cells (DCs) and conventional DC precursors
Since the first observations by Demetds et al, who initially identified human lung DC subsets through the BDCA markers previously applied to characterize blood DCs [55], understanding pulmonary DC subtypes has improved only in the last few years. Both genomic and functional studies have shown that human epithelial-associated DCs can be divided into four major subpopulations: plasmacytoid DCs (pDCs), cDC2 CD1c+, Conventional DC1 (cDC1) CD141+, and monocyte-derived DCs (mo-DCs) [36,37,38, 41]
Summary
Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating fatal lung disease that usually remains refractory to treatment [1,2,3], with an estimated median survival of 2 to 5 years from the first diagnosis. In the last two decades, disease incidence has steadily increased, varying from 2.8 to 19 cases per 100 .000 people per year in Europe and North America, respectively [1]. Disease behavior is highly variable, with associated comorbidities potentially exerting a detrimental impact on prognosis [4, 5]. The current availability of anti-fibrotic drugs (i.e., nintedanib and pirfenidone) has improved patients’ short-term life expectancy through the slowdown of the lung function decline and the reduction of hospitalization rate and episodes of acute exacerbation [6]
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