DNAX-activated protein 12 (DAP12) is a key transmembrane adaptor protein containing an immunoreceptor tyrosine-based activation motif. DAP12 associates with a broad spectrum of cell surface receptors, including triggering receptors expressed on myeloid cells (TREM1 and TREM2), myeloid DAP12-associating lectin-1 (MDL-1), sialic acid-binding immunoglobulin-like lectin 15 (Siglec15), killer cell immunoglobulin-like receptor (KIR), NKG2C/CD94, and NKp44. They form a sophisticated signaling network that precisely regulates cellular activation, differentiation, and the balance between pro-inflammatory and anti-inflammatory responses. DAP12 is predominantly expressed in innate immune cells, including monocytes/macrophages, microglia, osteoclasts, and natural killer (NK) cells, where it governs key processes like cytokine production, cytoskeletal remodeling, and cytotoxic activity. Dysregulation of DAP12 signaling has been implicated in the pathogenesis of multiple immune-related inflammatory diseases, such as multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. In these conditions, DAP12 contributes to either protective or pathological outcomes depending on the receptor complex and microenvironment. This review provides a comprehensive overview of the structural characteristics of DAP12, its interaction with relevant receptors, and its specific functions in various cell types and immune-mediated inflammation.

The gut microbiota plays a fundamental role in maintaining host health by regulating immune function, epithelial barrier integrity, and metabolic homeostasis. Disruption of microbial community structure (also known as dysbiosis) and altered host-microbiota interactions can shift microbial composition and metabolite production, promote immune dysregulation, and contribute to the initiation and persistence of chronic inflammation. Eicosanoids, a class of signaling lipid mediators derived from arachidonic acid , are essential modulators of acute and chronic inflammatory responses. Emerging evidence highlights a bidirectional interplay between the microbiota and eicosanoid pathways as a hallmark of chronic inflammation. Microbial taxa and their metabolites regulate arachidonic acid availability, eicosanoid biosynthesis, and receptor signaling in host cells. In turn, host-derived eicosanoids shape the gut environment, influencing the gut microbiota and host health state. This self-reinforcing loop drives key features of chronic inflammatory diseases, including a shift toward pro-inflammatory eicosanoid profiles, a relative deficiency of anti-inflammatory or pro-resolving lipid mediators, and microbiota dysbiosis. In this review, we summarize recent advances in the mechanisms underpinning microbiota-eicosanoid crosstalk, outline its contribution to chronic inflammatory diseases, and discuss the therapeutic potential of targeting this bidirectional axis.

TNF-alpha inhibtors represent an established option for autoimmune disorders such as rheumatoid arthritis, psoriasis and chronic-inflammatory bowel diseases as well as for granulomatous diseases including sarcoidosis. Their primary mode of action is antagonistic, blocking the interaction of TNF-alpha with its receptors TNFR1 and TNFR2. Currently five TNF-alpha inhibitors are clinically used: infliximab, adalimumab, golimumab, certolizumab and etanercept.In rare cases TNF-alpha inhibitors may induce sarcoidosis through a paradoxical reaction. This phenomenon is observed most frequently during treatment with etanercept, although the underlying mechanisms remain unclear. The clinical presentation of TNF-alpha inhibitor-induced sarcoidosis closely resembles that of idiopathic sarcoidosis and is characterized by a heterogeneous, inflammatory and granulomatous disease pattern with affection of multiple organ systems. Depending on the causative active agent, a differing distribution of clinical manifestations may occur.From a diagnostic perspective, laboratory analyses and the histological confirmation of the affected organ demonstrating epithelioid cell granulomas are essential. The cornerstone of therapy is the immediate discontinuation of the triggering TNF-α inhibitor. In selected cases, adjunctive systemic corticosteroid therapy may be considered. With timely recognition and appropriate management, the prognosis is generally favourable.

Fatigue is common in persons with Crohn's disease, negatively impacting quality of life in both active and remitted disease state. Neural correlates of fatigue in Crohn's disease are understudied, particularly relative to the separate impacts of physical, cognitive, and psychosocial fatigue. The potential moderating role of cortical complexity on the relationship between disease activity and fatigue has yet to be examined.

Inflammatory and autoimmune diseases are now understood to be significantly influenced by the intricate interactions between the microbiome and host physiology. This review investigates the function of epigenetic dysregulation in microbiome-host interaction and its consequences for health and disease. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNA-associated regulation, are key mechanisms that control gene expression without altering the underlying DNA sequence. Microbial metabolites and community composition alterations can cause disruptions in these epigenetic processes, resulting in dysregulated immune responses and the initiation of chronic inflammatory conditions. In particular, the diversity of gut microbiota alters host epigenetic patterns, affecting T cell differentiation, inflammatory modulation, and tissue homeostasis. Aberrant epigenetic modifications contribute to the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by promoting inflammation and autoimmunity. Similarly, gut microbiota dysbiosis has been implicated in the development and progression of inflammatory bowel disease (IBD). Identifying the reciprocal interaction between epigenetic alterations and microbiome dynamics provides unique insights into therapeutic options targeted at restoring microbial homeostasis to prevent disease progress. Consequently, understanding the intricacies of epigenetic dysregulation in microbiome-host interactions represents a significant sector in biomedical research and highlights the promise for precision medicine approaches in treating inflammatory and autoimmune diseases. The potential for microbiome-based therapies to affect host epigenetic landscapes requires additional research, paving the way for innovative therapeutic paradigms targeted at improving host resilience and restoring immunological balance. The purpose of this review is to synthesize current knowledge on how epigenetic dysregulation and microbiome-host interactions drive inflammatory and autoimmune diseases and to highlight emerging therapeutic opportunities.

Alterations of the gut microbiome have been reported in central nervous system demyelinating diseases. While the gut microbiome in pediatric multiple sclerosis (MS) has been studied, the role of the gut microbiome in other pediatric-onset acquired demyelinating syndromes (ADS) remains unknown. We compared the gut microbiome composition between myelin oligodendrocyte glycoprotein antibody-positive (MOG+) and antibody-negative (MOG-) participants with pediatric-onset ADS.

Emerging evidence suggests that low-carbohydrate diet (LCD) may exert beneficial effects across multiple autoimmune diseases (AIDs), yet their underlying mechanisms remain insufficiently elucidated and clinical evidence is still limited. This review provides a comprehensive synthesis of mechanistic insights, current clinical findings, and translational perspectives on LCD interventions in AIDs. Mechanistically, LCDs reprogram energy metabolism by shifting immune cell bioenergetics from glycolysis toward fatty acid oxidation and ketone utilization, thereby modulating inflammatory pathways such as NF-κB and the NLRP3 inflammasome. LCDs also reshape the gut microbiota and its metabolites, influencing intestinal barrier integrity and systemic immune responses, while epigenetic regulation-including histone deacetylase inhibition and DNA methylation-further stabilizes regulatory T cell identity and restrains pro-inflammatory gene expression. Clinically, encouraging outcomes have been observed in type 1 diabetes, psoriasis, and multiple sclerosis, whereas evidence in systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease remains scarce and heterogeneous. Importantly, existing data indicate that the optimal dietary pattern may differ across disease contexts, and LCDs are not uniformly superior to alternative dietary strategies. Current challenges include risks of nutrient deficiencies, uncertainties regarding long-term safety, variability in individual responses, and the lack of adequately powered randomized controlled trials. Moving forward, integrative research combining multi-omics, precision nutrition, and disease-specific dietary frameworks is needed to delineate responders, clarify mechanisms, and establish standardized protocols. Collectively, this review provides a structured framework for understanding the mechanistic basis and clinical potential of LCDs in AIDs, and outlines future directions for their safe and effective clinical translation.

Autoimmune diseases (AIDs) are chronic, heterogeneous disorders that are often diagnosed after irreversible tissue damage and treated with broad immunosuppression that fails to deliver durable remission. Nanotechnology offers opportunities to sense early immune perturbations and to deliver interventions with molecular, cellular and organ-level precision. Here we synthesize advances from 2015 to 2025 in nano-enabled diagnosis and therapy for rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, type 1 diabetes, psoriasis and selected rare AIDs. On the diagnostic side, nano-optical and electrochemical biosensors, nano-enhanced imaging probes, and liquid-biopsy platforms for extracellular vesicles and cell-free nucleic acids improve sensitivity, stratification and longitudinal monitoring, while wearable and point-of-care devices extend assessment into home and community settings. We relate these technologies to concrete clinical scenarios and highlight performance metrics such as limit of detection, sample volume, and clinical sensitivity/specificity. Therapeutically, we review stimuli-responsive and ligand-targeted nanocarriers for small molecules and biologics, tolerogenic nanoparticles and exosomes, mRNA-lipid nanoparticle "inverse vaccines", and microneedles or tissue-nanotransporter systems for local gene and cytokine modulation. We summarize emerging clinical trial data and currently marketed nanomedicines for autoimmune indications, linking formulation design to efficacy and safety readouts. Across platforms, we outline design principles connecting physicochemical properties to biodistribution and immune interactions, and we discuss manufacturability, long-term safety and regulatory hurdles that govern translation. Collectively, these advances, together with emerging AI and digital twin frameworks, illustrate how nanotechnology can support earlier diagnosis, more precise and tolerogenic interventions, and progress toward durable, personalized remission in AIDs.

PFAS are a group of persistent organic pollutants, that bioaccumulate and are associated with negative health effects. Reviews have suggested that the most critical effects of PFAS are on the immune system, but little is known of effects on development of autoimmunity. Our objective was to map and summarize available evidence concerning exposure to any PFAS and development/presence of autoimmunity, in humans and animals. We assessed studies reporting potential associations between PFAS exposure and autoimmune disease and/or autoantibodies. We searched MEDLINE, Embase, CENTRAL, Scopus, and Web of Science (02.15.2024) and conducted complimentary searches. Results were presented descriptively and we categorized autoimmune diseases and autoantibodies into relevant outcome groups. 51 studies were included, distributed in the following groups: Autoimmune thyroid disease, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, celiac disease, other diseases and autoantibodies. Cross-sectional studies were most common, limiting opportunities for causal inference. 33 studies showed associations between higher PFAS and increased risk of autoimmunity, while nine studies found lower PFAS associated with increased autoimmunity risk. The results suggest that PFAS have negative health impacts with strongest evidence for celiac and inflammatory bowel disease, weaker evidence for rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes mellitus. No clear indications of association with autoimmune thyroid disease. The majority of the studies showed an association between PFAS and autoimmunity. There is a need for more longitudinal and dose-response studies, to improve our understanding of individual autoimmunity outcomes in the future.Protocol registration: OSF.io (https://doi.org/10.17605/OSF.IO/3FEVQ).