Bacillus Calmette-Guérin-induced interleukin-10 inhibits S100A8/A9 production and hinders development of T helper type 1 memory in mice.

Tuberculosis caused by Mycobacterium tuberculosis (M.tb) is one of the main causes of human death in the world. Bacillus Calmette-Guérin (BCG) provides limited protection in adolescents and adults. To explore the factors reducing efficacy of BCG vaccine, we assess the impacts of interleukin (IL)-10 and alarmins S100A8/A9 on T-cell memory. We found that BCG-induced IL-10 inhibited production of S100A8/A9 in human peripheral blood mononuclear cells (PBMCs) and murine splenocytes. S100A9 deficiency inhibited IFN-γ production by CD4+ T cells in the early phase of BCG immunization and hindered the development of effector memory T helper type 1 (Th1) cells, while IL-10 deficiency promoted Th1 memory and blocking IL-10 signaling enhanced Th1 protective recall response against M.tb. IL-10 inhibited the binding of transcription factor CCAAT enhancer binding protein beta to S100a8/a9 promoter leading to S100A8/A9 reduction. S100A8/A9 heterodimer enhanced the IFN-γ production via receptor for advanced glycation end products signaling in CD4+ T cells. Our results demonstrate a hurdle to development of Th1 memory after BCG immunization and clarify the mechanism of the regulation of Th1 memory by IL-10 and S100A8/A9.

Free thyroid hormone: Methods and standardization.

Free thyroid hormone (FTH) serves as the preferred indicator for the clinical assessment of thyroid function, mainly encompassing free thyroxine and free triiodothyronine. The immunoassay commonly employed in the clinical setting exhibits certain unresolvable deficiencies. The results of over 5,500 clinical laboratories for FTH from China in 2024 demonstrated that the outcomes of immunoassay were not comparable, with robust CVs calculated in accordance with ISO 13528 ranging from 13.82% to 21.42%. Establishing reference methods is an important tool to achieve accurate and comparable results of free hormones. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) holds a distinct advantage in the precise detection of small molecules, and two reference methods for free thyroxine based on LC-MS/MS are included in the JCTLM list. This article conducts a comprehensive review of the detection methods and standardization of FTH. It presents the metabolism of thyroid hormones, the significance of detection, the techniques, and application examples of free thyroid hormone assays, and deliberates on the current status, prospects, and recommendations for the standardization of FTH assays. Immunoassay and LC-MS/MS, as significant techniques for FTH detection, are predominantly emphasized in the case references. Ultrafiltration and equilibrium dialysis, which are utilized to separate FTH, are also addressed. This article aims to discuss the status quo of FTH detection and clarify the advantages of LC-MS/MS in FTH detection, propose that LC-MS/MS can be utilized as an auxiliary validation method or alternative method in clinical applications, and offer suggestions for the standardization of testing results.