Extract

Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive disease of pulmonary fibrosis [1, 2]. In the 20th century, IPF was considered a chronic inflammatory disease characterised by the accumulation of inflammatory cells in the alveoli in response to key chemokines, triggering persistent damage to lung tissue and consequent pathological scarring [3]. This pathophysiological model was the driver of therapeutic approaches, relying on corticosteroids, immunosuppressants and antioxidants [4]. However, intense mechanistic studies since the early 21st century and, eventually, the failure of the PANTHER trial [5], prompted the establishment of a novel pathophysiological model. This latter is supported by strong genetic insights [6] and indicates that IPF mainly develops in susceptible individuals of advanced age, characterised by the premature senescence of type 2 pneumocytes, the exhaustion of their stem cell function, and the emergence of atypical alveolar epithelial cells mediating aberrant communication with fibroblasts [7–9]. Although inflammation no longer takes centre stage in this revised paradigm, immune alterations, including autoimmune markers [10] and abnormal chemokine secretion [11], underscore a crucial involvement of immune mediators in the crosstalk between epithelial and mesenchymal compartments in IPF.

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