Food allergy (FA) has received increased attention in recent years. Multiple studies have highlighted the crucial role of short-chain fatty acids (SCFAs) in the development of IgE-mediated FA. Here, a case-control approach was employed to analyze SCFAs profiles in children with FA, while an ovalbumin (OVA)-sensitized mouse model was utilized to explore the underlying mechanism by which SCFAs mitigate FA. Children with food-sensitized tolerance (FST) (n = 20) or FA (n = 20), and healthy controls (HC) (n = 20) were recruited to analyze SCFAs profiles. The HC group exhibited higher SCFAs levels in fecal samples than the FST, FA, and FST + FA groups. Data from an OVA-sensitized mouse model showed that butyrate exhibited a more significant effect on reducing allergic reactions compared to other SCFAs. Compared to the negative control group, OVA-induced oxidative stress (OS) triggered excessive Notch signaling activation, which subsequently impaired both tight junctions integrity and mucosal barrier function in murine intestinal epithelial cells (IECs). Gut dysbiosis induced mucus layer erosion, thereby elevating IECs exposure to food antigens and OS, which potentiated Notch signaling activation. However, butyrate counteracted this loop by restoring microbiota structure and suppressing reactive oxygen species (ROS)/Notch cascades. Strikingly, low-dose butyrate (0.25-1 mM) protected rat small intestine crypt epithelial cells (IEC-6) by inhibiting ROS, whereas high-dose (2-5 mM) exacerbated oxidative injury and triggered activation of Notch signaling. Our study revealed the potential molecular mechanisms through which butyrate alleviates food allergy, providing a potential therapeutic strategy for its management.
© 2025 The Author(s). iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.

Obesity is a rapidly increasing global health issue, which is associated with glucose and insulin resistance. Phosphodiesterase type 5 (PDE5) inhibitors (PDE5i) are known for their ability to enhance blood flow and vascular stability and are widely used to treat conditions such as erectile dysfunction, pulmonary hypertension, heart failure, and cancer. However, studies investigating the role of PDE5i in alleviating obesity and metabolic diseases remains unclear. Therefore, we investigated the effects of PDE5i on obesity and metabolic disorders in diet-induced obese mice and its underlying mechanisms.
PDE5i was administered to high-fat diet (HFD)-fed C57BL/6J mice for 6 to 7 weeks. Body weight and food intake were measured weekly, and baseline metabolic rates, physical activity, and glucose and insulin tolerance tests were assessed during PDE5i administration. Macrophages and T-cells in the gonadal white adipose tissue (gWAT) were analyzed by flow cytometry. Vascular stability and blood flow in gWAT were analyzed via immunostaining and in vivo live imaging. RAW264.7 cells and bone marrow-derived macrophages were used to determine immunoregulatory effects of PDE5i.
In HFD-fed mice, PDE5i administration significantly enhanced systemic insulin sensitivity and AKT phosphorylation in gWAT. PDE5i reduced the M1/M2 ratio of gWAT macrophages of obese mice. These phenomena were associated with enhanced blood flow to the gWAT. In vitro experiments revealed that PDE5i suppressed lipopolysaccharide-induced proinflammatory cytokine production and increased the mRNA expression of genes associated with M2 polarization.
PDE5i plays a role in regulating adipose tissue inflammation and thus holds promise as a therapeutic agent for metabolic enhancement.

Asthma is a chronic inflammatory respiratory disease characterized by recurrent breathing difficulties caused by airway obstruction and hypersensitivity. Although there is diversity in their specific mechanisms, microRNAs (miRNAs) have a significant impact on the development of asthma. Currently, the contribution of miR-130b-3p to asthma remains elusive. The goal of this study was to examine whether miR-130b-3p attenuates house dust mite (HDM)-induced asthma through High-mobility group box protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/mitochondrial fission protein (DRP1) signaling pathway. We elucidate that miR-130b-3p can bind to the HMGB1 3'UTR, attenuating HMGB1 mRNA and protein levels, and nucleo-cytoplasmic translocation of HMGB1. We observed that miR-130b-3p agomir or HMGB1 CKO attenuated HDM-induced airway inflammation and hyperresponsiveness, and decreased Th2-type cytokines in bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes. Further, HMGB1 CKO contributes to alleviating Th2 inflammation in AT-II cells (CD45.2-/CD31-/Epcam-+/proSP-C+/MHC-II+) from lung single cell suspensions of asthmatic mice by flow cytometry. Our findings identified miR-130b-3p as a potent regulator in asthma that exerts its anti-inflammatory effects by targeting HMGB1 and the subsequent HMGB1/TLR4/DRP1axis, presenting a prospective novel therapeutic avenue for asthma management.
© 2024. The Author(s).

The goal of therapeutic cancer vaccines and immune checkpoint therapy (ICT) is to promote T cells with anti-tumor capabilities. Here, we compared mutant neoantigen (neoAg) peptide-based vaccines with ICT in preclinical models. NeoAg vaccines induce the most robust expansion of proliferating and stem-like PD-1+TCF-1+ neoAg-specific CD8 T cells in tumors. Anti-CTLA-4 and/or anti-PD-1 ICT promotes intratumoral TCF-1- neoAg-specific CD8 T cells, although their phenotype depends in part on the specific ICT used. Anti-CTLA-4 also prompts substantial changes to CD4 T cells, including induction of ICOS+Bhlhe40+ T helper 1 (Th1)-like cells. Although neoAg vaccines or ICTs expand iNOS+ macrophages, neoAg vaccines maintain CX3CR1+CD206+ macrophages expressing the TREM2 receptor, unlike ICT, which suppresses them. TREM2 blockade enhances neoAg vaccine efficacy and is associated with fewer CX3CR1+CD206+ macrophages and induction of neoAg-specific CD8 T cells. Our findings highlight different mechanisms underlying neoAg vaccines and different forms of ICT and identify combinatorial therapies to enhance neoAg vaccine efficacy.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Atherosclerosis represents a chronic inflammatory condition in arterial walls, where local immune cells significantly contribute to disease progression. This study employed various in situ immunological techniques to investigate the specific roles of aortic dendritic cell (DC) subsets in atherosclerotic animal models, distinguishing between normal and diseased immune contexts. Our findings revealed that aortic DCs, particularly the cDC1 subset, played a critical role in facilitating CD8+ T cell activation through antigen presentation. Additionally, atherosclerosis-induced increases in GM-CSF levels enhanced CCR7 expression on aortic monocyte-derived DCs, promoting their recruitment and IL-12 production for Th1 differentiation. Notably, immunizing pre-atherosclerotic mice with DC-presented antigens or transferring aortic DCs from atherosclerotic mice resulted in accelerated disease onset. This research elucidates the adaptive immune functions of aortic DCs, offering insights into the cellular mechanisms driving aortic inflammation and potential therapeutic targets for atherosclerosis management.
© 2024 The Author(s).