Dendritic Cells Are the Intriguing Players in the Puzzle of Idiopathic Pulmonary Fibrosis Pathogenesis

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.

Keywords: cancer; dendritic cells; idiopathic pulmonary fibrosis; immunity; immunotherapy.

Figure 1

Dendritic cells (DCs) derive from hematopoietic stem cells in the bone marrow. Progenitor cells give rise in the final step to Common Derived Progenitors (CDPs) that differentiate in the blood circulating DC subtypes and in lung tissue DC subsets.

Figure 2

Dendritic cells (DC) are located in the lung interstitium and alveoli, where they act as sentinel cells. Any imbalance of their frequency distribution and functional status may have significant consequences in disease pathogenesis. Emerging evidence suggests that plenty of local factors along with different arrays of chemo-cytokines can modulate DCs maturation in the lung of patients affected by idiopathic pulmonary fibrosis, thus affecting their tolerogenic or immunogenic properties.