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Macrophages play a central role in orchestrating immune responses to foreign materials, which are often responsible for the failure of implanted medical devices. Material topography is known to influence macrophage attachment and phenotype, providing opportunities for the rational design of “immune‐instructive” topographies to modulate macrophage function and thus foreign body responses to biomaterials. However, no generalizable understanding of the inter‐relationship between topography and cell response exists. A high throughput screening approach is therefore utilized to investigate the relationship between topography and human monocyte–derived macrophage attachment and phenotype, using a diverse library of 2176 micropatterns generated by an algorithm. This reveals that micropillars 5–10 µm in diameter play a dominant role in driving macrophage attachment compared to the many other topographies screened, an observation that aligns with studies of the interaction of macrophages with particles. Combining the pillar size with the micropillar density is found to be key in modulation of cell phenotype from pro to anti‐inflammatory states. Machine learning is used to successfully build a model that correlates cell attachment and phenotype with a selection of descriptors, illustrating that materials can potentially be designed to modulate inflammatory responses for future applications in the fight against foreign body rejection of medical devices. Using an unbiased screen of an algorithm generated topographical library in combination with machine learning, this study identifies topographies which instruct both the attachment and polarization of human macrophages in the absence of exogenous cytokines.

Aging is the primary risk factor for many neuromuscular (NM) diseases that impair motor and cognitive function. Transplantation of young muscle‐derived stem/progenitor cells (MDSPCs) has shown remarkable therapeutic potential across a range of age‐related diseases, primarily through paracrine mechanisms. In this study, secretome profiling of young MDSPCs revealed a unique enrichment of pro‐angiogenic and immunomodulatory proteins compared to their aged counterparts. Our systemic transplantation experiments also demonstrate that young MDSPCs activate biological pathways linked to these secreted factors, providing strong mechanistic evidence of their contribution to the reversal of age‐associated NM decline at molecular, structural, and functional levels. Systemic transplantation of young MDSPCs into naturally aged mice enhanced motor function and reduced anxiety‐like behavior. Structural improvements in aged NM tissues were partially mediated by phosphorylating protein sites involved in muscle neovascularization and regulation of blood–brain barrier integrity in the motor cortex. Paracrine signaling from young MDSPCs enhanced the endogenous regenerative capacity of aged tissues, with effects sustained for up to 2 months post‐transplantation. Overall, this study elucidates the molecular basis of MDSPC‐mediated NM rejuvenation and provides a foundation for developing novel protein–based therapies to combat age‐related functional decline. Young multipotent muscle‐derived stem/progenitor cells (MDSPCs) secrete a unique profile of pro‐angiogenic and immunomodulatory proteins that are diminished with age. Systemic transplantation of young MDSPCs into naturally aged mice activates pathways in neuromuscular tissues, enhancing health and driving molecular, structural, and functional rejuvenation. Diagram was created with BioRender.com.

Background Delayed hypersensitivity reactions, such as allergic contact dermatitis (ACD), present distinct patterns across age groups. While age‐related immune changes are well‐documented, their impact on patch test outcomes and allergen sensitization in elderly individuals remains underexplored. Objectives This study assessed age‐related differences in allergen sensitization and immune response in ACD by comparing patch test reactions between elderly individuals (≥ 65 years) and younger adults (18−40 years). In addition, findings were also compared with a similar study conducted between 1997 and 2001. Methods A retrospective cohort study analysed a total of 2377 patients who underwent patch testing at the University of Padua's Dermatology Clinic from 2006 to 2019. The study included 709 elderly and 1668 younger adults, evaluating standard allergen series for differences in sensitization based on age, sex and affected body sites. Results Elderly patients had a lower rate of positive patch test reactions (62.6%) compared to younger individuals (71.5%) and exhibited fewer cases of multiple contact allergies. Allergic reactions were more frequently localized to the face in the elderly, while younger adults showed more cases of hand dermatitis. The intensity of allergic reactions was generally milder in the elderly. Strong reactions were significantly more frequent among younger individuals, especially for nickel. Sensitization patterns differed, with younger adults more commonly reactive to nickel and cobalt, while balsam of Peru and neomycin were more prevalent in the elderly. Conclusions Although aging is associated with a decline in immune responsiveness, elderly individuals remain significantly sensitized to allergens such as balsam of Peru and neomycin. Compared to data from 1997 to 2001, both age groups show an increased prevalence of sensitization and multiple contact allergies, suggesting a temporal trend. These findings highlight the importance of considering age‐related immune changes when diagnosing and managing ACD in older patients. Summary The study investigates age‐related differences in allergic contact dermatitis to understand how immunosenescence affects allergen sensitization and patch test reactivity. Elderly individuals show lower patch test positivity, milder reactions and distinct allergen sensitization patterns compared to younger adults (e.g., increased reactivity to balsam of Peru and neomycin). Immunosenescence alters allergic contact dermatitis presentation, requiring age‐specific diagnostic approaches and personalized management strategies for older patients.

AAs have become interesting feed ingredients to be used in functional fish feeds as not only are they protein building blocks, but they also participate in several other key metabolic processes. In the present study, a comprehensive analysis of transcriptomics, hematology, and humoral immune parameters (plasma and skin mucus) were measured twice over the course of the feeding trial (four weeks). Plasma antiprotease activity increased in fish fed Thr compared to those fed the CTRL and Tau treatments, regardless of sampling time. The bactericidal activity in skin mucus decreased in fish fed Tau and His treatments compared to those fed the CTRL diet after two weeks. The membrane IgT (mIgT) was upregulated in fish fed Tau after four weeks, while C-type lectin domain family domain 10 member (clec10a) was downregulated in fish fed Thr after two weeks of feeding. By comparing the molecular signatures of head-kidney by means of a PLS-DA, it is possible to visualize that the main difference is between the two sampling points, regardless of diet. Altogether, these results suggest that dietary supplementation with these AAs at the tested levels causes mild immune-modulation effects in gilthead seabream, which should be further studied under disease challenge conditions.

Febrile infection related epilepsy syndrome (FIRES) is a rare presentation of refractory status epilepticus with immune dysregulation as a potential pathologic mechanism. Despite promising results from second‐line immunomodulators, approximately 30% remain refractory to treatment. We describe two children with FIRES who were unable to wean from anesthetic infusions with immunomodulatory treatment and subsequently received concurrent intrathecal dexamethasone and anakinra/tocilizumab as escalation of therapy. Following the initiation of this combined regimen, anesthetic infusions were decreased while maintaining seizure freedom. These cases demonstrate proof of principle that a multi‐modal approach may be beneficial and should be considered in the treatment of FIRES.

Chronic hepatitis B (CHB) remains a global health challenge, necessitating innovative therapeutic strategies. Enhancing the body's immune response against the hepatitis B virus (HBV) emerges as a fundamental strategy for achieving a functional cure. While acupuncture has shown potential in immune modulation, its specific anti-HBV effects are not well understood. This study evaluates the potential of electroacupuncture (EA) in HBV infection and explores its underlying immunological mechanisms using a mouse model. HBV-infected mice were established using the high-pressure hydrodynamic method and divided into four groups: normal saline (NS), EA, sham EA (SE), and tenofovir disoproxil fumarate (TF), with n = 6 per group. During treatment, blood was collected every Sunday via the orbital sinus to monitor HBV DNA, HBsAg, and HBeAg levels. Transcriptomics and metabolomics analyses were employed to unearth clues regarding EA's anti-HBV mechanism. Validation of these mechanisms included splenic T-cell flow analysis, Western blotting, RT-qPCR, immunofluorescence, and ELISA. Serum HBV DNA levels decreased by 1.10, 0.19, and 1.98 log IU/mL in the EA, SE, and TF-treated mice, respectively, compared to the NS. Concurrently, the hepatic HBV DNA levels decreased by 1.09, 0.24, and 2.03 log IU/mL. EA also demonstrated superior inhibition of HBV antigens, with serum HBeAg levels decreasing by 43.86%, 8.74%, and 8.03%, and serum HBsAg levels decreasing by 28.01%, 0.26%, and 9.39% in the EA, SE, and TF groups, respectively. Further analysis through transcriptomics and metabolomics revealed that EA's anti-HBV effects primarily hinge on immune modulation, particularly the IFN-γ/JAK/STAT pathway and taurine metabolism. EA also increased the ratio of splenic CD8 CD69 and CD8 IFN-γ T-cells while upregulating key proteins in the JAK/STAT pathway and cytokines associated with antiviral immunity. EA manifests inhibitory effects on HBV, particularly in antigen suppression, with its mode of action intricately linked to the regulation of IFN-γ/JAK/STAT.

Immune cells and commensal microbes in the human intestine constantly communicate with and react to each other in a stable environment in order to maintain healthy immune activities. Immune system-microbiota cross-talk relies on a complex network of pathways that sustain the balance between immune tolerance and immunogenicity. Probiotic bacteria can interact and stimulate intestinal immune cells and commensal microflora to modulate specific immune functions and immune homeostasis. Growing evidence shows that probiotic bacteria present important health-promoting and immunomodulatory properties. Thus, the use of probiotics might represent a promising approach for improving immune system activities. So far, few studies have been reported on the beneficial immune modulatory effect of probiotics. However, many others, which are mainly focused on their metabolic/nutritional properties, have been published. Therefore, the mechanisms behind the interaction between host immune cells and probiotics have only been partially described. The present review aims to collect and summarize the most recent scientific results and the resulting implications of how probiotic bacteria and immune cells interact to improve immune functions. Hence, a description of the currently known immunomodulatory mechanisms of probiotic bacteria in improving the host immune system is provided.

Mesenchymal stem cells (MSCs) can be derived from various adult tissues with multipotent and self‐renewal abilities. The characteristics of presenting no major ethical concerns, having low immunogenicity and possessing immune modulation functions make MSCs promising candidates for stem cell therapies. MSCs could promote inflammation when the immune system is underactivated and restrain inflammation when the immune system is overactivated to avoid self‐overattack. These cells express many immune suppressors to switch them from a pro‐inflammatory phenotype to an anti‐inflammatory phenotype, resulting in immune effector cell suppression and immune suppressor cell activation. We would discuss the mechanisms governing the immune modulation function of these cells in this review, especially the immune‐suppressive effects of MSCs.

Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19. Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig. 89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19. The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.

Nanoparticle (NP) is an emerging tool applied in the biomedical field. With combination of different materials and adjustment of their physical and chemical properties, nanoparticles can have diverse effects on the organism and may change the treating paradigm of multiple diseases in the future. More and more results show that nanoparticles can function as immunomodulators and some formulas have been approved for the treatment of inflammation-related diseases. However, our current understanding of the mechanisms that nanoparticles can influence immune responses is still limited, and systemic clinical trials are necessary for the evaluation of their security and long-term effects. This review provides an overview of the recent advances in nanoparticles that can interact with different cellular and molecular components of the immune system and their application in the management of inflammatory diseases, which are caused by abnormal immune reactions. This article focuses on the mechanisms of interaction between nanoparticles and the immune system and tries to provide a reference for the future design of nanotechnology for the treatment of inflammatory diseases. Graphical Abstract