IPF represents a dire and relentless disease marked by irreversible lung tissue scarring and excessive extracellular matrix (ECM) deposition within the organ’s parenchyma. This pathology culminates in the deterioration of healthy epithelial tissue, compromised gas exchange, and heightened lung rigidity [1]. IPF stands as the predominant form of idiopathic interstitial pneumonia, with its incidence steadily increasing over time. In Europe, estimates suggest a prevalence of 2.8 to 18 cases per 100,000 individuals annually. Predominantly affecting men, this condition rarely manifests in individuals under the age of 50, with the median age at diagnosis typically around 65 years old [2]. IPF displays significant clinical diversity, yet its prognosis remains bleak, typically resulting in a median survival of 3–4 years. Considering these factors, IPF represents a considerable financial burden, with direct treatment expenses averaging approximately 25,000 USD per person per year- surpassing the costs associated with conditions like breast cancer and various other serious illnesses [3]. Diagnosing IPF presents challenges, but a combination of symptoms including shortness of breath, coughing, and abnormalities observed in chest imaging can aid in identification [4]. Despite the elusive nature of its precise etiology, research has highlighted the crucial role of alveolar epithelial type 2 (AT2) cells in the pathogenesis and progression of IPF [5]. Alveolar epithelial cells are indispensable constituents of pulmonary function, crucial in both health and disease. These cells are categorized into two types: Type I Alveolar Cells, which encompass approximately 95 % of the alveolar surface and are responsible for efficient gas exchange by facilitating rapid diffusion between air and blood, and Type II Alveolar Cells, cuboidal in shape and interspersed among type I cells, recognizable by their lamellar bodies. These cells secrete surfactant, vital for maintaining alveolar stability and preventing lung collapse, thus ensuring optimal respiratory function [6]. ATII cells synthesize pulmonary surfactant (PS), a vital substance for mitigating alveolar surface tension, upholding alveolar stability, and enhancing pulmonary compliance. PS composition comprises 90 % lipids, encompassing phospholipids and cholesterol, and 10 % proteins. The malfunction of PS has been proposed to lead to alveolar collapse potentially, subsequently promoting the deposition of the ECM within the alveolar septa and contributing to the development of PF [7]. Repetitive damage to the alveolar epithelium, marked by alterations such as cellular proliferation, hyperplasia, and aberrant activation, has been implicated in the pathogenesis of PF. This pathological cascade is attributed to the disruption of epithelial-mesenchymal crosstalk, resulting in the senescence of pulmonary epithelial cells and subsequent dysregulated interactions with fibroblasts [8]. Moreover, ECM holds a pivotal role in fibrosis pathogenesis, involving elements like collagens, proteoglycans, and glycoproteins like elastin, fibronectin, and laminin within the alveolar and interstitial compartments [9]. In 2014, the Food and Drug Administration (FDA) sanctioned Nintedanib and Pirfenidone for IPF treatment due to their demonstrated ability to decelerate disease advancement [10]. Despite these advancements and the improved prognosis they offer, IPF persists as an incurable condition, owing in part to its nuanced and insufficiently understood origins [11].

At every phase of fibrosis, innate and adaptive immune reactions are present. The significance of inflammation in the origins of IPF is a subject of debate, occasionally regarded as a secondary outcome of fibrosis. IPF has been shown through preclinical data to be influenced by both innate and adaptive immune responses [12]. Dysfunction in epithelial cells triggers multifaceted interactions with mesenchymal, immune, and endothelial cells through intricate signaling pathways, consequently initiating the activation of fibroblasts and myofibroblasts within the immune cell environment [11]. As immune cells transition from a quiescent state to an activated state, as observed during instances of infection or inflammation, they undergo metabolic reprogramming to adapt their cellular metabolism in response to the energy demands imposed by the microenvironment [13]. Metabolism drives various biological processes in an adult organism, fueling essential programs such as development, proliferation, differentiation, and the execution of effector functions by cells and tissues [14]. The metabolic dynamics or imbalances within fibroblasts, epithelial cells, immune cells, and diverse cellular populations contribute significantly to the development of PF. Advancements in comprehending the intricate interplay between metabolic reprogramming and the activation of immune cells across various diseases have unveiled novel therapeutic avenues. Emerging strategies involve the modification of intracellular metabolism in immune cells to target specific metabolic pathways. Notably, certain drugs with metabolic-targeting properties, including metformin, dimethyl fumarate, methotrexate, and rapamycin, have been successfully employed in treating inflammatory and autoimmune diseases. These medications exert their effects by regulating key metabolic processes such as glucose, fatty acid, and nucleotide metabolism. Consequently, the manipulation of distinct metabolic targets presents a promising approach for effectively managing inflammation in conditions like PF [15].