Monocytes can differentiate into macrophages (Mo-Macs) or dendritic cells (Mo-DCs). The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the differentiation of monocytes into Mo-Macs, while the combination of GM-CSF/interleukin (IL)-4 is widely used to generate Mo-DCs for clinical applications and to study human DC biology. Here, we report that pharmacological inhibition of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the presence of GM-CSF and the absence of IL-4 induces monocyte differentiation into Mo-DCs. Remarkably, we find that simultaneous inhibition of PPARγ and the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) induces the differentiation of Mo-DCs with stronger phenotypic stability, superior immunogenicity, and a transcriptional profile characterized by a strong type I interferon (IFN) signature, a lower expression of a large set of tolerogenic genes, and the differential expression of several transcription factors compared with GM-CSF/IL-4 Mo-DCs. Our findings uncover a pathway that tailors Mo-DC differentiation with potential implications in the fields of DC vaccination and cancer immunotherapy.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Rearrangements that drive ectopic MEF2C expression have recurrently been found in patients with human early thymocyte progenitor acute lymphoblastic leukemia (ETP-ALL). Here, we show high levels of MEF2C expression in patients with ETP-ALL. Using both in vivo and in vitro models of ETP-ALL, we demonstrate that elevated MEF2C expression blocks NOTCH-induced T cell differentiation while promoting a B-lineage program. MEF2C activates a B cell transcriptional program in addition to RUNX1, GATA3, and LMO2; upregulates the IL-7R; and boosts cell survival by upregulation of BCL2. MEF2C and the Notch pathway, therefore, demarcate opposite regulators of B- or T-lineage choices, respectively. Enforced MEF2C expression in mouse or human progenitor cells effectively blocks early T cell differentiation and promotes the development of biphenotypic lymphoid tumors that coexpress CD3 and CD19, resembling human mixed phenotype acute leukemia. Salt-inducible kinase (SIK) inhibitors impair MEF2C activity and alleviate the T cell developmental block. Importantly, this sensitizes cells to prednisolone treatment. Therefore, SIK-inhibiting compounds such as dasatinib are potentially valuable additions to standard chemotherapy for human ETP-ALL.

The term probiotic has been defined by experts as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. Probiotics are, thus, by definition, live microorganisms, and the viability of probiotics is a prerequisite for certain benefits, such as the release of metabolites at the site or adhesion properties, for example. However, some semi-active or non-replicative bacterial preparations may retain a similar activity to the live forms. On cosmetic, lysates or fractions are generally used. Topically applied Vitreoscilla filiformis extract has shown to have some similar biological activity of probiotics in the gut, for example, regulating immunity by optimisation of regulatory cell function, protecting against infection, and helping skin barrier function for better recovery and resistance. Due to their mode of action and efficacy, V. filiformis extract (lysate including membrane and cytosol) may be considered as non-replicative probiotic fractions, and this review article presents all its properties.
Copyright © 2021 Gueniche, Liboutet, Cheilian, Fagot, Juchaux and Breton.

Probiotics are live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. Semiactive, non-replicating bacteria or extracts used in dermocosmetics have interesting properties for skin quality. Vitreoscilla filiformis is cultured by a fermentation process to obtain an extract. It is considered as a probiotic fraction and topical application of this extract has shown activity to strengthen the skin physical barrier function and maintain good homeostasis of skin defenses. Vichy volcanic mineralizing water (VVMW) is a pure, highly mineralized water that has been shown to strengthen the skin against exposome aggressions. This manuscript reviews properties of probiotic fractions used in skin care, especially studies on an extract of V. filiformis grown in a medium containing VVMW (VfeV) and evaluated in combination with VVMW. Skin barrier function: In normal human epidermal keratinocyte cultures, the combination of 10% VVMW and 0.002% VfeV significantly increased transglutaminase, filaggrin, involucrin, claudin-1, and zonula occludens-1 in comparison with the controls. Antimicrobial peptide defenses: The combination of 16.7% VVMW and 0.1% VfeV increased the expression of β-defensin-4A and S100A7. Skin immune defense functions: In lipopolysaccharide-stimulated peripheral blood mononuclear cells, the combination of 16.7% VVMW and 0.1% VfeV down-regulated IL-8, TNF-α, IL-12/IL-23p40, and increased IL10 and IL-10/IL-12 ratio compared to the control. Additionally, the combination of 79% VVMW plus 5% VfeV protected Langerhans cells in skin explants exposed to ultraviolet radiation. In conclusion, the combination of VfeV plus VVMW has properties to strengthen the skin barrier by stimulating skin differentiation and tight junctions, biochemical defenses by stimulating antimicrobial peptides, and cellular immune defenses by increasing the IL-10/IL-12 ratio and by protecting Langerhans cells challenged by ultraviolet radiation.
© 2021 European Academy of Dermatology and Venereology.