Immune cells crosstalk Pathways, and metabolic alterations in Idiopathic pulmonary fibrosis

[Display omitted] •Immune cells are involved in pathogenesis which leads to metabolic alterations in IPF.•Immune cells prevent IPF until a threshold, beyond which they cause inflammation and progress disease.•Pro-inflammatory-fibrotic axis by promoting EMT through the different signaling pathways.•Adipokine dysregulation leads to low-grade inflammation in adipose tissue and leads to fibrosis.•IPF patients and BLM-induced preclinical data showed metabolic changes driven by immune cells in PF. Idiopathic pulmonary fibrosis (IPF) presents a challenging progression characterized by lung tissue scarring and abnormal extracellular matrix deposition. This review examines the influence of immune responses, emphasizing their complex role in initiating and perpetuating fibrosis. It highlights how metabolic pathways modulate immune cell function during IPF. Immune cell modulation holds promise in managing pulmonary fibrosis (PF). Inhibiting neutrophil recruitment and monitoring mast cell levels offer insights into PF progression. Low-dose IL-2 therapy and regulation of fibroblast recruitment present potential therapeutic avenues, while the role of innate lymphoid cells (ILC2s) in allergic lung inflammation sheds light on disease mechanisms. The review focuses on metabolic reprogramming’s role in shaping immune cell function during IPF progression. While some immune cells use glycolysis for pro-inflammatory responses, others favor fatty acid oxidation for regulatory functions. Targeting specialized pro-resolving lipid mediators (SPMs) presents significant potential for managing fibrotic disorders. Additionally, it highlights the pivotal role of amino acid metabolism in synthesizing serine and glycine as crucial regulators of collagen production and exploring the interconnectedness of lipid metabolism, mitochondrial dysfunction, and adipokines in driving fibrotic processes. Moreover, the review discusses the impact of metabolic disorders such as obesity and diabetes on lung fibrosis. Advocating for a holistic approach, it emphasizes the importance of considering this interplay between immune cell function and metabolic pathways in developing effective and personalized treatments for IPF.