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

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.

Mitochondrial-mediated nuclear remodeling and macrophage polarizations: A key switch from liver fibrosis to HCC progression.

Liver fibrosis is a significant health burden worldwide and has emerged as the leading cause of Hepatocellular carcinoma (HCC) incidence. Mitochondria are the dynamic organelles that regulate the differentiation, survival, and polarization of macrophages. Nuclear-DNA-associated proteins, micro-RNAs, as well as macrophage polarization are essential for maintaining intracellular and extra-cellular homeostasis in the liver parenchyma. Dysregulated mitochondrial coding genes (ETS complexes I, II, III, IV, and V), non-coding RNAs (mitomiRs), and nuclear alteration lead to the production of reactive oxygen species (ROS) and inflammation which are implicated in the transition of liver fibrosis into HCC. Recent findings indicated the protecting effect of E74-like factor 3/peroxisome proliferator-activated receptor-γ (Elf-3/PPAR-γ). HDAR-y inhibits the deacetylation of PPAR-y and maintains the PPAR-y pathway. Elf-3 plays a tumor suppressive role through epithelial-mesenchymal transition-related gene and zinc finger E-box binding homeobox 2 (ZEB-2) domain. Additionally, the development of HCC includes the PI3K/Akt/mTOR and transforming Growth Factor ß (TGF-ß) pathway that promotes the Epithelial-mesenchymal transition (EMT) through Smad/Snail/Slug signaling cascade. In contrast, the TLR2/NOX2/autophagy axis promotes M2 polarization in HCC. Thus, a thorough understanding of the mitochondrial and nuclear reciprocal relationship related to macrophage polarization could provide new research opportunities concerning diseases with a significant impact on liver parenchyma towards developing liver fibrosis or liver cancer. Moreover, this knowledge can be used to develop new therapeutic strategies to treat liver diseases.