Fig. 3

Exosome-mediated intercellular crosstalk in organ dysfunction. Exosomes mediate crucial intercellular communication between releasing and recipient cells, playing a significant role in the progression of sepsis-related organ dysfunction. a In acute lung injury, epithelial cells play a crucial role by releasing exosomes abundant in proteins and miRNAs, which induce macrophages to polarize towards the M1 phenotype, amplifying pulmonary inflammation. On the other hand, M1 macrophage-derived exosomal APN/CD13 and TNF exacerbate lung injury by promoting programmed cell death in lung epithelial cells. b In acute liver injury, hepatocytes release exosomes containing miR-192-5p, prompting macrophages to adopt the M1 phenotype. This polarization leads to the release of inflammatory mediators like iNOS, IL-6, and TNF-α into the hepatic microenvironment, worsening hepatic cell dysfunction. Additionally, exosomes from M1 macrophages containing miR-103-3p promote the proliferation and activation of hepatic stellate cells, further contributing to liver injury. c In acute cardiac dysfunction, exosomes from M1 macrophages containing miR-155 inhibit fibroblast proliferation, thus contributing to cardiac damage. Conversely, exosomes from M2 macrophages containing miR-148a suppress inflammasomes, reducing myocardial injury. MSCs further protect the heart by releasing exosomes laden with miR-22 and miR-221, which counteract cardiomyocyte apoptosis. d In acute kidney injury, tubular epithelial cells damaged by oxidative stress secrete exosomes with miR-19b-3p and miR-23a, inducing macrophages to polarize into the M1 phenotype. This exacerbates renal inflammation and contributes to the progression of kidney damage. APN/CD13 aminopeptidase N, TNF tumor necrosis factor, miRNAs microRNAs, M1 type 1 macrophage, M2 type 2 macrophage, iNOS inducible nitric oxide synthase, IL-6 interleukin 6, TNF-α tumor necrosis factor-α, MSCs mesenchymal stem cells, CASP3 caspase-3, PDGF platelet-derived growth factor, CCL2 C-C motif chemokine ligand 2