B cell tolerance is critical for preventing autoimmunity, yet the mechanisms by which B cells discriminate self from non-self antigens remain incompletely understood. While early findings emphasize the role of classical antigen-mediated BCR signaling strength by varying antigen formats, emerging evidence highlights the importance of mechanical cues during antigen recognition. This review explores how mechanosensitive ion channels, particularly Piezo1, contribute to B cell activation and tolerance by integrating physical forces at the immune synapse. We discuss how membrane-bound and particulate antigens induce mechanotransduction through Piezo1, promoting enhanced B cell responses by extracellular calcium influx. Additionally, we consider the differential roles of Piezo1 in various physiological contexts, including shear stress, tissue migration, and substrate stiffness. Understanding mechanosensor-mediated signaling in coordination with other pathways such as antigen recognition, T cell help, or cytokine signaling expands our knowledge of B cell biology and introduces a new paradigm for modulating humoral immunity in health and disease.

Solute carrier (SLC) transporters are membrane proteins that facilitate the movement of various substrates, such as nutrients and organic or inorganic ions, across cellular membranes. Recent studies underscore the critical roles of SLC transporters in regulating cancer metabolism, immune evasion, and the tumor microenvironment. Increasing evidence suggests that the SLC39 and SLC30 families of zinc transporters, responsible for importing and exporting zinc into and out of the cytoplasm, respectively, modulate intracellular zinc distribution and signaling and may play a role in cancer initiation or progression. In this review, we discuss the functional roles of these zinc transporters in different cancer types and examine potential mechanisms linking zinc metabolism with oncogenic pathways that contribute to malignancy.

Colorectal cancer (CRC) is a major health concern and understanding its molecular characteristics is crucial for improving its diagnosis and treatment. Here, we present a comprehensive analysis utilizing RNA-sequencing (RNA-seq) data and clinical information from Korean patients with CRC. Differential gene expression analysis identified significant changes in gene expression between tumor and normal tissues. Gene Set Enrichment Analysis (GSEA) revealed dysregulated pathways associated with tumor progression. Furthermore, using CMScaller, we successfully stratified CRC tissues into distinct molecular subtypes. Upon reviewing the public consensus molecular subtype (CMS) signature, it was confirmed that it shares similar biological characteristics with the existing CRC. Additionally, biological characteristics of the group that could not be classified using CMScaller were found to resemble those of CMS2. Finally, distinguishing characteristics were observed between the tumor and normal groups when analyzed from an immunological perspective. Patients with CRC were checked for immunotherapy responsiveness, and those who clinically responded to immunotherapy were identified. Survival analysis confirmed that certain microsatellite stable (MSS) samples were responsive to immunotherapy and showed a relatively better prognosis. Furthermore, analysis of various immune cell types to identify genes involved in the response to immunotherapy revealed that RORC, NOS2, and KLRK1 are potential candidate genes. Our findings provide valuable insights into the molecular landscape of CRC in the Korean population and underscore the potential for integrating RNA-seq data with clinical information to improve cancer research and patient care. Immunotherapy was found to be effective in Korean patients with CRC.

Obesity is a major global health crisis, yet the molecular mechanisms underlying adult-onset metabolic dysfunction remain incompletely understood. The tubby mouse is a foundational genetic model of maturity-onset obesity; however, the specific tissues and cell populations responsible for its metabolic phenotype have long remained elusive. Here, we demonstrate that the loss of tubby disrupts the coordinated regulation of energy intake and expenditure, leading to a sustained positive energy balance. Using cell-type-specific genetic tools, we identified MC4R-expressing and VGLUT2-expressing neurons as essential sites of tubby function. We found that tubby acts through the combined contribution of these neuronal populations, as selective deletion in either MC4R or VGLUT2 neurons is sufficient to phenocopy key features of the global Tub mutant. Together, these findings establish tubby as a central neuronal regulator of systemic energy homeostasis and define an excitatory MC4R-VGLUT2 circuit that governs feeding behavior and metabolic output.

Hepcidin (encoded by the HAMP gene), produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. Its dysregulation contributes to various iron-related metabolic disorders. Cereblon (CRBN) has been implicated in metabolic regulation, while estrogen-related receptor gamma (ESRRG) is known to govern energy homeostasis and mitochondrial function. In this study, we demonstrate a novel CRBN-ESRRG signaling pathway that mediates endoplasmic reticulum (ER) stress-induced hepatic HAMP expression. In mice and primary hepatocytes exposed to tunicamycin-induced ER stress, gene expression and biochemical analyses revealed significant increases in the transcript levels of hepatic Crbn, Esrrg, and Hamp. Correspondingly, hepcidin protein levels were elevated, accompanied by reduced serum iron levels and increased cellular iron levels, consistent with hepcidin-mediated regulation of iron distribution. Overexpression of Crbn enhanced ESRRG expression and increased hepatic hepcidin production, while knockdown of either Crbn or Esrrg attenuated this response. Chromatin immunoprecipitation assays demonstrated enhanced recruitment of ESRRG to the Hamp promoter. Collectively, these findings identify a CRBN-ESRRG regulatory axis that drives hepatic HAMP expression under ER stress and suggest a potential therapeutic target for ER stress-associated metabolic and iron disorders.