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Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-α) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups. [ABSTRACT FROM AUTHOR]

Darier disease (DD) is a rare autosomal dominant genodermatosis characterized by erythematous papules and plaques mainly involving sebaceous areas, such as the face, chest and back. Skin microbiome plays an essential role in maintaining skin homeostasis. A disturbed skin microbiome may contribute to the exacerbation of DD. We investigated the bacterial composition of two predilectional sites in DD patients and healthy individuals. We also measured the microbiome composition of deeper skin layers, where diversity was significantly reduced compared to the superficial layer of the skin from the same area. The microbiome of DD patients at lesional sites differed from that of non-lesional skin areas; moreover, non-lesional sites were different from those of the controls. Lesional areas were dominated by Staphylococcus species, such as S. aureus, S. epidermidis, S. hominis, S. sciuri, and S. equorum. However, levels of Cutibacterium acnes (formerly Propionibacterium acnes) and C. acnes subspecies defendens were significantly lower in lesional sites than in non-lesional sites. A significant decrease was measured in the levels of these two bacteria between non-lesional and control samples. Our findings may indicate that alterations in the skin microbiome could contribute to the inflammation of skin lesions in DD., (© 2024. The Author(s).)

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs -- also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-alpha) reprogram macrophages by releasing prostaglandin E(2) that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.