Picrasidine S Induces cGAS-Mediated Cellular Immune Response as a Novel Vaccine Adjuvant.

New adjuvants that trigger cellular immune responses are urgently needed for the effective development of cancer and virus vaccines. Motivated by recent discoveries that show activation of type I interferon (IFN-I) signaling boosts T cell immunity, this study proposes that targeting this pathway can be a strategic approach to identify novel vaccine adjuvants. Consequently, a comprehensive chemical screening of 6,800 small molecules is performed, which results in the discovery of the natural compound picrasidine S (PS) as an IFN-I inducer. Further analysis reveals that PS acts as a powerful adjuvant, significantly enhancing both humoral and cellular immune responses. At the molecular level, PS initiates the activation of the cGAS-IFN-I pathway, leading to an enhanced T cell response. PS vaccination notably increases the population of CD8+ central memory (TCM)-like cells and boosts the CD8+ T cell-mediated anti-tumor immune response. Thus, this study identifies PS as a promising candidate for developing vaccine adjuvants in cancer prevention.

IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.

Eosinophils regulate intra-adipose axonal plasticity.

Sympathetic innervation regulates energy balance, and the nerve density in the adipose tissues changes under various metabolic states, resulting in altered neuronal control and conferring resilience to metabolic challenges. However, the impact of the immune milieu on neuronal innervation is not known. Here, we examined the regulatory role on nerve plasticity by eosinophils and found they increased cell abundance in response to cold and produced nerve growth factor (NGF) in the white adipose tissues (WAT). Deletion of Ngf from eosinophils or depletion of eosinophils impairs cold-induced axonal outgrowth and beiging process. The spatial proximity between sympathetic nerves, IL-33-expressing stromal cells, and eosinophils was visualized in both human and mouse adipose tissues. At the cellular level, the sympathetic adrenergic signal induced calcium flux in the stromal cells and subsequent release of IL-33, which drove the up-regulation of IL-5 from group 2 innate lymphoid cells (ILC2s), leading to eosinophil accretion. We propose a feed-forward loop between sympathetic activity and type 2 immunity that coordinately enhances sympathetic innervation and promotes energy expenditure.

Neuroimmune regulation of white adipose tissues.

The white adipose tissues (WAT) are located in distinct depots throughout the body. They serve as an energy reserve, providing fatty acids for other tissues via lipolysis when needed, and function as an endocrine organ to regulate systemic metabolism. Their activities are coordinated through intercellular communications among adipocytes and other cell types such as residential and infiltrating immune cells, which are collectively under neuronal control. The adipocytes and immune subtypes including macrophages/monocytes, eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2s), T and B cells, dendritic cells (DCs), and natural killer (NK) cells display cellular and functional diversity in response to the energy states and contribute to metabolic homeostasis and pathological conditions. Accumulating evidence reveals that neuronal innervations control lipid deposition and mobilization via regulating lipolysis, adipocyte size, and cellularity. Vice versa, the neuronal innervations and activity are influenced by cellular factors in the WAT. Though the literature describing adipose tissue cells is too extensive to cover in detail, we strive to highlight a selected list of neuronal and immune components in this review. The cell-to-cell communications and the perspective of neuroimmune regulation are emphasized to enlighten the potential therapeutic opportunities for treating metabolic disorders.

Panicle-Shaped Sympathetic Architecture in the Spleen Parenchyma Modulates Antibacterial Innate Immunity.

The nervous system can modulate the body's immunity. However, how efferent neural signals reach out to control the local immunity remains incompletely understood. Here, we report the ImmuView procedure for whole-tissue 3D assessment of neural innervations in the intact immune organs of adult mice. This advanced imaging technique revealed an intricate, panicle-shaped sympathetic architecture in the parenchyma of the spleen but not other immune organs, including the lymph nodes, Peyer's patch, and thymus. In contrast, we observed the minimal presence of parasympathetic innervations in the parenchyma of all of the classic immune organs examined. Specific deletion of the TrkA receptor abolishes the sympathetic architecture in the spleen and such genetic ablation significantly enhanced the spleen antibacterial innate immunity. Moreover, the sympathetic neurotransmitter norepinephrine could inhibit the LPS-elicited innate immunity cell-intrinsically via ß2-adrenergic receptor signaling. This study exemplifies the key link that specifically connects the efferent sympathetic signal with the spleen innate immunity.

[Application of glycosyl fluorides in the study on glycosidases].

Glycosyl fluorides are becoming increasingly important molecules for the study on glycosidases. Firstly, glycosyl fluorides act as substrates for glycosidases hydrolysis. Scecondly, the installation of fluorine elsewhere on the carbohydrate ring modifies the properties of the glycosyl fluoride so that the resultant compounds act as mechanism-based inhibitors to label enzymes in the active site, allowing identification of the catalytic nucleophile. Furthermore, glycosyl fluorides also act as donors for transglycosylation by retaining glycolides. Finally, glycosyl fluorides of the wrong anomeric configuration could be used by retaining glycosidase mutants such as glycosynthases and thioglycosynthases to synthesize carbohydrate with high yields(normally 60% to approximately 90%). Fundamental and applied research in biology, glycobiology and nanobiotechnology would benefit from the possibility of synthesizing tailor-made oligo-/poly-saccharides.

[Hydrogen photoproduction from acetate by Rhodopseudomonas palustris].

Based on the characteristics of metabolism of photosynthetic bacteria and the major kinds of organic compounds produced in wastewater degradation, eleven kinds of organic compounds were chosen for hydrogen photoproduction using Rhodopseudomonas palustris Z strain. The maximal volumetric H2 productivity was obtained using acetate as the sole carbon source and electron donor. The kinetics of cell growth and H2 liberation, and the influences of several major limiting factors on photoevolution of H2 were examined using acetate as carbon source. It was shown that hydrogen production was partially correlated with cell growth. The medium composition of the preculture, the preculture time, and inoculation volume were confirmed to have big effects on hydrogen photoevolution. The time delay of H2 production was evidently shortened using the inoculum of late exponential growth phase or stationary phase using ammonium sulfate as nitrogen source or with the inoculum of middle exponential growth phase using glutamate as the nitrogen source. The identity of temperature and light intensity for H2 evolution and cell growth has significant potential application in the technology of splitting organic acid into H2 by photosynthetic bacteria. The concentrations of acetate and glutamate in the medium affected hydrogen photoevolution and cell growth significantly. The productivity of H2 increased with substrate concentrations when substrate concentrations of sodium acetate and sodium glutamate were lower than 70 mmol/L and 15 mmol/L, respectively. Hydrogen production was inhibited but the cell growth was faster when the concentration of sodium glutamate over 15 mmol/L due to forming free NH4+. The highest rate of hydrogen production was 19.4 mL.L-1.h-1 using 30 mmol/L of sodium acetate as hydrogen donor under the standard conditions, respectively. The optimal conditions for hydrogen production were 35-37 degrees C, 6000-8000 lx and pH 7.3-8.3. The effects of oxygen and inoculation volume on photoproduction of hydrogen were also discussed.