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This document is an editorial from the International Journal of Molecular Sciences that discusses the regulatory roles of inflammation and inflammasomes in liver diseases. It explains that while inflammation is a natural immune response that protects the body, chronic inflammation can lead to various diseases, including liver diseases. The article highlights the importance of the priming and triggering steps in the inflammatory response and the role of inflammasomes in activating inflammation. It also presents several studies that explore the regulatory roles of flavonoids, chemokines, reactive nitrogen species, and neutrophil infiltration in liver diseases. Additionally, the editorial discusses the impact of SARS-CoV-2 infection on patients with advanced chronic liver disease. The authors hope that this special issue provides insights into the role of inflammation in liver diseases and contributes to the development of novel therapeutics. [Extracted from the article]

TNFR1 and TNFR2 have received prominent attention because of their dominance in the pathogenesis of inflammation and autoimmunity. TNFR1 has been extensively studied and primarily mediates inflammation. TNFR2 remains far less studied, although emerging evidence demonstrates that TNFR2 plays an antiinflammatory and immunoregulatory role in various conditions and diseases. Herein, we report that TNFR2 regulates macrophage polarization, a highly dynamic process controlled by largely unidentified intracellular regulators. Using biochemical copurification and mass spectrometry approaches, we isolated the signaling molecule 14-3-3[epsilon] as a component of TNFR2 complexes in response to progranulin stimulation in macrophages. In addition, 14-3-3[epsilon] was essential for TNFR2 signaling-mediated regulation of macrophage polarization and switch. Both global and myeloid-specific deletion of 14-3-3[epsilon] resulted in exacerbated inflammatory arthritis and counteracted the protective effects of progranulin-mediated TNFR2 activation against inflammation and autoimmunity. TNFR2/14-3-3[epsilon] signaled through PI3K/Akt/mTOR to restrict NF-[kappa]B activation while simultaneously stimulating C/EBP[beta] activation, thereby instructing macrophage plasticity. Collectively, this study identifies 14-3-3[epsilon] as a previously unrecognized vital component of the TNFR2 receptor complex and provides new insights into the TNFR2 signaling, particularly its role in macrophage polarization with therapeutic implications for various inflammatory and autoimmune diseases with activation of the TNFR2/14-3-3[epsilon] antiinflammatory pathway., Introduction Rheumatoid arthritis (RA) is a common chronic autoimmune condition characterized by inflammatory joint disease (1), resulting from protracted inflammation of the synovial membrane. Macrophages are a major subset of [...]