Immuno, Volume 6, Issue 3 (September 2026) – 18 articles

Chronic low-grade inflammation (“inflammaging”) is epidemiologically linked to organ-specific aging, but tissue-resolved proteomic evidence remains limited. In this exploratory study, we used 4D-DIA proteomics to profile heart, liver, spleen, and kidney from mice given chronic LPS (0.1 µg/day i.p., 2 months) with or without ibuprofen co-treatment (0.02 mg/mL in drinking water). LPS exposure was associated with the most pronounced proteome changes in kidney (489 DEPs) and liver (293), followed by spleen (170) and heart (135). Intersecting LPS-associated DEPs with the Aging Atlas database isolated aging-annotated proteins; within this subset, ibuprofen co-treatment corresponded to opposite-direction changes in a tissue-dependent manner (n = 3 mice/group): kidney (8/13, 61.5%), liver (4/9, 44.4%), spleen (1/8, 12.5%), and heart (0/5). Functional enrichment of these oppositely-regulated aging-annotated proteins revealed kidney-specific enrichment in DNA/RNA-binding and antioxidant activities, and liver-specific enrichment in growth factor receptor signaling and kinase regulation. STRING networks showed a kidney-specific interaction cluster centered on Sod2, Sirt3, and Jun, whereas liver showed only a discrete Egfr–Gstp1 pair. Notably, aging-annotated DEPs functioned as network hubs, directly connecting to approximately 50% of non-aging-annotated DEPs in liver and 43% in kidney. Collectively, these exploratory findings identify tissue-specific proteomic correlates within the aging-annotated protein subset—particularly in kidney and liver—generating hypotheses for future validation in larger experimental cohorts. Full article

Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory disorder characterized by recurrent epithelial injury and incomplete inflammatory resolution. Cellular senescence and the senescence-associated secretory phenotype may help explain how stromal cells sustain this inflammatory circuit. This narrative review critically evaluates direct and indirect evidence linking senescence to OLP. A focused search of PubMed/MEDLINE, Scopus, and Web of Science through 31 July 2026 identified evidence localizing senescence-associated signatures predominantly to PDGFRα-positive mesenchymal cells. The available multimodal study also reported enhanced CXCL12–CXCR4 and extracellular matrix–CD44 communication toward CD8-positive T cells and showed that conditioned medium from experimentally induced senescent fibroblasts increased lymphoid-cell activation and keratinocyte injury in non-oral and immortalized cell models. Earlier studies of p16, p21, p53, altered cyclin-dependent kinases, oxidative/nitrative DNA damage, and SASP-compatible cytokines provide supportive evidence but are insufficient to establish cellular senescence. We hypothesize a feed-forward model in which persistent oxidative and cytokine stress induces senescence in mesenchymal and possibly epithelial cells. A context-dependent SASP may recruit and activate cytotoxic lymphocytes, promote basal keratinocyte damage, and propagate further cellular stress. Further progress will require spatially resolved multi-marker validation and functional testing in primary oral-cell models before biomarker-guided clinical trials can be considered. These advances may ultimately support the development of novel targeted therapies for OLP. Full article

Background/Objective: Previous studies on the association between chronic rhinosinusitis (CRS) and allergic rhinitis (AR) have mostly focused on the general population, and much less on patients with CRS requiring surgical treatment. This study aimed to investigate the frequency of perennial and seasonal AR (PAR and SAR, respectively) among CRS patients in whom it was necessary to apply surgical treatment, including those with nasal polyps (CRSwNP) and those without (CRSsNP). Methods: A three-year retrospective study from a single center included CRS patients with indications for surgical treatment. The patients were not previously treated surgically. Several clinical parameters were considered: frequency of AR, PAR, SAR, SAR+PAR, asthma, and gastroesophageal reflux disease (GERD). Total serum IgE, percentage of eosinophils in peripheral blood, and Lund–Mackay computed tomography (CT) score (LMS) were also determined. Correlation analyses were performed to assess the relationships among the clinical parameters, while multivariable binary logistic regression analysis was performed to determine their independent associations with the outcome and to identify the best independent predictor. Results: A total of 155 patients with CRS were considered. Over 70% were patients with CRSwNP. AR was significantly more prevalent in patients with CRSwNP (p = 0.049), with PAR being the more common form (p = 0.035). Also, GERD and asthma were more common in CRSwNP (p = 0.01 and p = 0.001, respectively). The strongest correlation was found between total serum IgE and percentage of eosinophils (rho = 0.776; p < 0.001), then between percentage of eosinophils and LMS (rho = 0.760; p < 0.001), as well as between total IgE and LMS (rho = 0.695; p < 0.001). Binary logistic regression analysis identified LMS as the only independent statistically significant predictor for CRSwNP (OR = 1.381, p < 0.001) among all numerical parameters. Conclusions: The results suggest a better association between PAR and CRS, especially with CRSwNP. Asthma and GERD are also highly associated, primarily with CRSwNP. LMS is the best independent predictor for the presence of CRSwNP. Full article

Although cryoablation of tumor tissue is known to induce systemic antitumor immune responses, the underlying mechanisms remain poorly understood, and therapeutic efficacy is often unpredictable. During cryoablation, the cryoprobe creates a temperature gradient, resulting in a central zone of lethal tissue destruction and a periphery characterized by sub-lethal injury. In this peripheral zone, cells undergo programmed cell death triggered by thermal shock and ischemia. A widely cited, yet debated, hypothesis suggests that these apoptotic events in the tumor periphery may suppress the antitumor immune response. The purpose of this study was to experimentally test this hypothesis. We utilized the murine breast cancer cell line (4T1-Luc) and a panel of human cell lines (MCF-7, BT-20, BT-474, MDA-MB-231, MDA-MB-453, HBL-100). Following validation via flow cytometry using Annexin V-AF488, Rhodamine 123, TMRE, PI, and 7-AAD, we established −7 °C and −80 °C as temperature conditions that predominantly induce apoptosis and necrosis, respectively. These conditions were used to prepare cryo-treated 4T1-Luc cells for the vaccination of syngeneic mice. Ten days post-immunization, the efficacy of the treatment was evaluated in subcutaneous solid tumor and lung metastasis models by monitoring tumor growth, quantifying tumor-specific antibodies, performing histological analysis of tumor and lung tissues, and quantifying lung metastases via PCR and luciferase assays. Contrary to the initial hypothesis, our findings demonstrate that tumor cells undergoing sub-lethal cryoablation do not acquire immunosuppressive characteristics. Instead, they promote systemic antitumor immunity. Although antitumor immunity induced by apoptotic and necrotic tumor cells was comparable in a subcutaneous tumor model, vaccination with necrotic tumor cells proved more effective than vaccination with apoptotic cells in controlling lung metastasis formation. Full article

Chronic nasopharyngeal inflammation represents a state of persistent mucosal immune dysregulation within the nasopharynx, a key inductive site of upper airway immunity. In this review, we propose a hypothesis-generating conceptual framework in which disease progression reflects a sequential shift in dominant immune pathways—from early CD4⁺ T-cell-driven activation, through to T helper 17 (Th17)-mediated epithelial barrier dysfunction, and ultimately to CD8⁺ T-cell-mediated cytotoxic injury. These transitions are characterized by dynamic alterations in CD4/CD8 and Th17/Treg balance, contributing to epithelial fragility and sustained inflammatory activity. Beyond local pathology, prolonged inflammation may engage neuro-immune circuits, including vagal and neuroendocrine pathways, potentially linking mucosal immune activation to systemic physiological dysregulation. While several elements of this model are supported by existing knowledge in mucosal immunology, the integration of local and systemic immune processes remains partly hypothetical and requires further experimental validation. Epipharyngeal Abrasive Therapy (EAT) may represent a potential intervention within this framework, although its immunological mechanisms remain incompletely understood. However, the underlying mechanisms and clinical efficacy of EAT remain to be fully elucidated. This framework integrates local mucosal immune dynamics with potential systemic consequences and provides a conceptual basis for future investigations into chronic mucosal inflammation. It is intended as a hypothesis-generating conceptual review that integrates existing observations and proposes a conceptual framework to guide future mechanistic and clinical studies. Full article

Background: Takayasu arteritis (TA) is a large-vessel vasculitis with an incompletely understood pathogenesis, in which genetic factors are thought to play an important role. Cytokine-mediated immune pathways, particularly those involving Th1 and Th17 responses, have been implicated in the immunopathogenesis of TA, making cytokine gene polymorphisms plausible genetic susceptibility markers. Methods: Functional single-nucleotide polymorphisms in selected cytokine- and receptor-encoding genes (IL12B, IL23R, IL6, TNF, IL10, and CSF2) were analyzed in 33 patients with TA and 486 healthy Serbian controls using TaqMan genotyping assays. Allele and genotype frequencies were compared between groups. Results: A nominally significant association was observed only for IL12B rs3212227. The T allele and TT genotype were less frequent in patients compared with controls (71.21% vs. 82.02%, p = 0.037; 48.48% vs. 66.67%, p = 0.041, respectively), suggesting a potential protective effect. No significant associations were detected for polymorphisms in IL23R, IL6, TNF, IL10, or CSF2. Conclusions: Our findings support the potential role of IL12B in genetic susceptibility to Takayasu arteritis, while other examined cytokine gene polymorphisms showed no statistically significant association. These results highlight the importance of the IL-12/IL-23 axis in disease pathogenesis and suggest possible population-specific genetic effects. Further studies in larger and independent cohorts are warranted to validate these findings. Full article

Background: Cyclophosphamide (CTX)-induced immunosuppression involves systemic toxicity, splenic atrophy, and broad transcriptomic disruption. Icariin (ICA) has immunomodulatory activity, but the systems-level features associated with splenic recovery remain incompletely defined. Methods and Results: Male mice were assigned to control, CTX, and CTX plus ICA (20, 40, or 80 mg/kg) groups. Phenotypic measurements were integrated with splenic RNA sequencing, differential expression analysis, targeted gene-set analysis, and weighted gene co-expression network analysis (WGCNA). ICA produced dose-associated improvement in spleen index and body weight trajectory, with the most consistent phenotypic response at 80 mg/kg. Overall transcriptomic separation was supported by permutational multivariate analysis of variance (PERMANOVA) (F = 17.18, R² = 0.873, p < 0.001). WGCNA identified a recovery-associated turquoise module; Myb was assigned to this module, whereas Gata1 belonged to a distinct royalblue module. Complement and chemokine gene sets provided the strongest targeted enrichment evidence, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) confirmed dose-associated changes in selected innate immune transcripts. Marker-based lineage signatures indicated non-uniform recovery, including persistent depression of the B-cell signature. Conclusion: ICA-associated phenotypic recovery coincided with partial, non-uniform remodeling of splenic transcriptional programs. The Myb- and Gata1-associated findings are hypothesis-generating co-expression signals and do not establish transcription-factor binding or causality. Full article

Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal-recessive combined immunodeficiency marked by severe cutaneous viral infections, atopy with elevated IgE, malignancy, and early mortality without hematopoietic stem-cell transplantation (HSCT). Foundational syntheses predate the current transplant era and biologic therapy. Objective: It aims to provide an updated individual-patient-data (IPD) synthesis of DOCK8 deficiency cases reported from 2017 to 2026. Methods: Following PRISMA 2020 and PRISMA-IPD guidance, we searched PubMed/MEDLINE (with full Boolean strings provided for Embase, Scopus, Web of Science and Cochrane CENTRAL) for reports with extractable individual data on confirmed DOCK8 deficiency. Two-stage screening, Murad-2018 risk-of-bias assessment, random-effects Freeman–Tukey pooled proportions (with a random-intercept logistic model as a sensitivity analysis), and reconstructed Kaplan–Meier analyses were performed. Results: Of 360 records, 56 full texts were assessed, and 41 studies were included; 29 provided individual data for 64 patients from 22 countries, and 12 contributed aggregate data. Sixty-three potentially eligible reports were paywalled and could not be retrieved, and non-English reports were excluded, introducing possible retrieval and language bias. Consanguinity was reported in 40/43 (93%); the genotype spectrum was dominated by large deletions and splice/intronic variants. Eczema (72%), cutaneous viral infection (80%) and bacterial infection (64%) predominated. The pooled proportion alive at last reported follow-up was 87.3% (95% CI 81.1–92.6); this is a cross-sectional proportion over variable follow-up and is not a long-term survival estimate, as reconstructed age-specific Kaplan–Meier survival fell to approximately 53% by age 20 (exploratory analysis). Pooled malignancy prevalence was 10.6% (95% CI 3.4–20.7; I² = 66%), and pooled post-HSCT survival was 86.3% (95% CI 79.0–92.5). Conclusions: Contemporary reports reaffirm the severe infectious and malignant burden of DOCK8 deficiency and support HSCT as definitive therapy, alongside emerging biologic (dupilumab, siltuximab) and gene-directed strategies. Findings are constrained by reporting, retrieval and language bias and by reconstructed IPD; completion of the planned multi-database searches and independent second-reviewer verification are ongoing to finalise the evidence base. Full article

PNH is an acquired ultrarare disease caused by a somatic mutation of PIGA gene located at band 22 of the short arm of the X chromosome, which is unable to carry out the synthesis of glycosil-phosphatidyl-inositol. The loss of complement regulators CD55 and CD59 is associated with the lack of the protective complement regulators in RBCs that become highly susceptible to complement-mediated lysis. PNH is characterized by intravascular hemolysis, high prevalence of thrombotic events, and a variable degree of bone marrow failure. It may arise from aplastic anemia, myelodysplasia and myeloproliferative neoplasms. Recently, a new clinical variant of PNH has been reported, the so-called “ahemolytic white blood cell PNH”, which may be associated with thrombotic episodes. In 2006, the introduction of eculizumab therapy has revolutionized the treatment for PNH patients. More recently, ravulizumab, crovalimab, iptacopan, danicopan, and pegcetacoplan have been introduced in the marketplace, with short/medium-term data supporting their safety and effectiveness. However, no trial has directly compared the clinical outcomes of the new drugs, and also the inclusion criteria in the various phase 3 trials were different, making a comparison between them difficult and unsatisfactory. It is conceivable that artificial intelligence and machine learning-based scoring models may be crucial for predicting the effectiveness of the anti-complement therapy. Full article

RNA modifications act as crucial post-transcriptional regulators that fine-tune gene expression to modulate cell function. Among these, N6-methyladenosine (m⁶A) is the most prevalent RNA modification in eukaryotic cells, regulating several RNA metabolism pathways including RNA splicing, nuclear export, stability, and translation. These processes are particularly important in rapidly responding immune cells such as T cells, which require dynamic changes in gene expression to support differentiation and effector function. This review focuses on the interplay between immunity and epitranscriptomics and explores the direct and indirect effects of m⁶A modification on T cells. Specifically, we discuss the role of different writers, erasers, and readers in modulating CD4+ and CD8+ T cell homeostasis, differentiation, and function. In addition, we summarize current evidence linking m⁶A regulators to anti-tumor T cell responses. Finally, we discuss the recent advances in the field of m⁶A and immunotherapy by highlighting the potential of pharmacological modulation of m⁶A regulators in augmenting the efficacy of existing immune therapies. Collectively, by integrating emerging mechanistic and translational insights, this review highlights the pivotal role of m⁶A regulation in T cell biology and underscores its potential to optimize next-generation immunotherapies. Full article

Regulatory CD4+ T cells (Tregs) are essential for immune tolerance, tissue repair, and control of inflammation, but functional human Tregs cannot be identified reliably by a single protein. This targeted narrative review evaluates protein-level and proteomics-supported Treg signatures with explicit attention to species, sample source, analytical platform, validation strategy, and intended use. Primary human LC-MS/MS studies reveal pathway-level differences involving T-cell receptor signaling, metabolism, lysosomal activity, and lineage protection, whereas murine proteomic studies provide mechanistic candidates such as Themis1 but do not establish human biomarkers. CyTOF, functional single-cell protein profiling, spatially resolved protein imaging, and multi-omics further resolve phenotypic and tissue heterogeneity. Established CD25high/CD127low/FOXP3-based panels support enrichment and phenotyping; CTLA-4, ICOS, TIGIT, GITR, PD-1, chemokine receptors, suppressive enzymes, metabolic proteins, and emerging candidates report functional or tissue states but are not Treg-exclusive. Cancer currently provides the strongest tissue-level and prognostic evidence, whereas data in healthy aging, cardiovascular and metabolic disease, osteoarthritis, and neurodegeneration remain heterogeneous and mainly exploratory. Across contexts, validated diagnostic sensitivity, specificity, reference ranges, prospective clinical utility, and inter-laboratory reproducibility are largely absent. Treg immunoproteomics is therefore best regarded as a discovery and stratification framework rather than a standardized clinical diagnostic test. Full article

Neonatal calf diarrhea (NCD) is one of the most important problems of calf breeding across the world. It causes deaths in calves in the first 10 days of their life, and it is mainly caused by Escherichia coli(E. coli), Bovine Rotavirus (BRV) and Bovine Coronavirus (BCoV). The lack of vaccines with consistently high protective efficacy against the main causes of NCD makes disease control highly challenging. The current study aims to design a multi-epitope mRNA-based vaccine targeting the major pathogens responsible for NCD using immunoinformatic tools and molecular modeling approaches. BRV capsid protein VP6, BCoV Spike glycoprotein and E. coli F5 fimbrial protein were used as antigenic proteins to predict potential epitopes. Fifteen selected epitopes were linked with suitable linkers and conjugated with a built-in adjuvant, resulting in the design of a stable, antigenic and non-allergenic vaccine candidate against NCD pathogens. Furthermore, molecular docking analysis shows strong binding affinity between the vaccine candidate and the bovine toll-like receptors TLR2 and TLR4 at low energy and high stability. Based on these findings, the proposed multi-epitope vaccine represents a promising approach for the prevention and control of neonatal calf diarrhea and provides a solid scientific foundation for future experimental studies to validate its efficacy and safety in vivo. Full article

Immune checkpoint inhibitors (ICIs) are now being introduced into perioperative treatment for several solid tumors. This strategy is usually explained by tumor reduction before surgery or by the elimination of minimal residual disease (MRD) after surgery. However, these explanations may not be sufficient to understand why the timing of ICI treatment, especially before lymph node (LN) removal, is important. In this review, we discuss tumor-draining lymph nodes (tdLNs) from two different aspects. tdLNs are anatomical routes for regional and distant metastasis, but they are also sites where tumor antigens are presented and tumor-specific T cell responses are generated. In particular, preclinical and translational studies suggest that tdLNs may maintain stem-like or progenitor-exhausted T cells (TPEX) that can respond to PD-1 blockade and supply more differentiated exhausted T cells to tumor sites. However, current clinical trials of perioperative ICIs demonstrate therapeutic benefit in specific diseases and regimens, but do not directly establish tdLN preservation or tdLN-resident TPEX maintenance as the decisive mechanism of efficacy. We therefore present the tdLN-reservoir model as a hypothesis-generating framework rather than as a clinically validated basis for modifying lymph node management. We also discuss the possible roles of neoadjuvant and adjuvant ICI in relation to antigen flow, minimal residual disease, metastatic-site draining LNs, postoperative lymphatic dysfunction, and future immune-guided clinical trials. Importantly, current evidence does not support altering standard lymph node surgery or radiotherapy solely to preserve putative tdLN immune-reservoir function. Full article

The endometrial microbiome has been implicated in implantation success, and intrauterine peripheral blood mononuclear cell (PBMC) therapy has been proposed to improve endometrial receptivity; however, its effects on the endometrial microbial environment remain poorly understood. This prospective study evaluated changes in endometrial microbiome composition following PBMC therapy in 26 in vitro fertilization (IVF) patients. Paired endometrial biopsies were collected before and after intrauterine administration of autologous PBMCs, and 16S rRNA gene sequencing (V4–V5 region) was performed. Microbiome composition was analyzed at genus and species levels, and alpha and beta diversity metrics were compared between paired samples. No significant changes in microbial composition or diversity were observed across the entire cohort following treatment. However, patients with lower baseline Lactobacillus abundance exhibited greater microbiome responsiveness, showing larger increases in Lactobacillus after treatment. This association remained significant after adjustment for age and BMI (ρ = −0.457, p = 0.019; β = −0.367, p = 0.047). Moreover, subgroup analysis identified two distinct response patterns based on Lactobacillus dynamics: a Lactobacillus-increase group (n = 14) and a no-increase group (n = 12). Baseline Lactobacillus dominance (LD: >90% relative abundance) was less frequent in the increase group (14%) than in the no-increase group (50%). In Lactobacillus-increase patients, the median relative abundance rose from 17.6% to 95.5% (p < 0.001), 64% achieved LD, and Shannon and Simpson diversity indices decreased significantly (p = 0.04 and p = 0.02, respectively). In the no-increase group, Lactobacilli remained the most abundant taxon, and the diversity indices were unchanged following treatment. These findings suggest that baseline endometrial microbiome composition may influence responsiveness to PBMC therapy and could support future patient stratification strategies in IVF treatment. Whether these microbiome changes translate into improved clinical outcomes requires evaluation in future studies. Full article

Percutaneous coronary intervention (PCI) treats focal coronary obstruction by compressing plaque, injuring the vessel wall, and placing a metallic or bioresorbable scaffold. Most treated segments heal, but a small minority enter a prolonged, excessive, or unstable repair state that contributes to in-stent restenosis (ISR), in-stent neoatherosclerosis, and stent thrombosis (ST). Human evidence is strongest for delayed healing, uncovered struts, macrophage-rich neoatherosclerosis, and hypersensitivity-associated late thrombosis, whereas routine immune biomarker-guided care remains unsupported. The practical question addressed here is therefore not whether inflammation participates, which is established, but which immune signals, read together with intravascular imaging, could realistically change post-PCI management. The narrowed lumen is only the visible endpoint; beneath it sits vascular repair shaped by device-material exposure, local haemodynamics, and host immunity. Endothelial denudation and platelet activation initiate fibrin deposition, complement signalling, and release of damage-associated molecular patterns (DAMPs). Neutrophils, monocytes, and macrophages dominate early, followed by lymphocytes and vascular smooth muscle cells that remodel the repair compartment. Drug-eluting stents (DES) have markedly reduced early neointimal hyperplasia, yet selected late failures still involve delayed endothelial recovery, chronic peristrut inflammation, hypersensitivity, and neoatherosclerotic transformation. Immune biology is useful at the bedside only when interpreted with procedural context, device design, and patient phenotype. Imaging-defined endpoints and paired immune phenotyping are therefore needed to guide treatment by mechanism instead of angiography or isolated biomarkers. Full article

Chagas disease is a parasitic infection caused by Trypanosoma cruzi and remains an important public health problem with changing epidemiological patterns. Both the acute and chronic phases pose diagnostic and prognostic challenges due to the disease’s heterogeneous clinical course. Chronic inflammation and fibrosis associated with Chagas disease lead to anatomical and morphological changes, as well as increased release of inflammatory mediators. These factors may contribute to alterations in blood viscosity and hemorheological behavior. This study aimed to evaluate hemorheological properties and inflammatory cytokine levels in individuals with chronic Chagas disease. Blood samples from 18 individuals infected with T. cruzi and 15 uninfected controls were analyzed. Rheological parameters were measured using a rheometer, and cytokine levels were quantified by flow cytometry. The infected group had a mean age of 57.25 years, including both sexes. The mean time since laboratory diagnosis was 13 years. Hematological analysis demonstrated significant alterations in leukocyte subpopulations and erythrocyte-related parameters, including lymphocyte count, red blood cell indices, hemoglobin, hematocrit, and platelet-related markers. Blood samples from both groups demonstrated non-Newtonian fluid behavior and non-linear flow curves. However, individuals infected with T. cruzi presented significant alterations in blood viscosity compared to controls. Increased serum levels of IL-1β, IL-6, CXCL8 (IL-8), and IL-10 were also observed in infected individuals. The blood viscosity showed a significant positive correlation with CXCL8 (IL-8) and IL-10 levels. These findings suggest that cytokine-associated hemorheological alterations may contribute to the pathophysiology and clinical progression of chronic Chagas disease. Full article

Background: Neutrophil dysregulation drives inflammatory pathologies through mechanisms such as matrix metalloproteinase-9 (MMP-9) release. High-value bioprospecting of agro-industrial residues offers a sustainable strategy to identify novel bioactive compounds. In this study, the immunomodulatory effects of seed oils (SOs) obtained via supercritical fluid extraction from Passiflora edulis and Rubus glaucus byproducts on human neutrophil responses was evaluated. Methods: SO lipid profiles were characterized via GC-MS. Human neutrophils were isolated using Percoll gradients and treated with the SOs (10–50 µg/mL). Cytocompatibility was assessed via MTT and trypan blue assays. MMP-9 activity and ERK1/2/p38 phosphorylation were determined via zymography and Western blotting, respectively. Results of GC-MS revealed matrices rich in unsaturated lipids: R. glaucus SO was dominated by linoleic (50.02%) and α-linolenic (29.84%) acids, whereas P. edulis SO contained linoleic (58.91%) and oleic (19.75%) acids. Both oils were highly biocompatible up to 50 µg/mL. Both SOs significantly increased MMP-9 release; notably, R. glaucus induced a dose-dependent response and a potential priming effect at 10 µg/mL. Interestingly, neither oil induced the phosphorylation of ERK1/2 or p38. Conclusions: Supercritical fluid-extracted SOs from P. edulis and R. glaucus byproducts modulate early neutrophil responses by increasing MMP-9 release through pathways independent of classical MAPK phosphorylation. Further functional and in vivo validation is needed to clarify the precise regulatory roles of these specialized lipid matrices in human inflammation resolution and their potential as bioactive ingredients for nutraceutical or pharmaceutical applications. Full article

Circadian rhythms impose temporal organization on immune function, shaping host responses to infection, injury, and chronic disease. While transcriptional control by core clock components such as CLOCK and BMAL1 has been extensively characterized, this paradigm alone cannot explain the rapid and dynamic nature of immune signaling. Emerging evidence identifies post-translational modifications (PTMs)—including phosphorylation, ubiquitination, and acetylation—as critical regulators that confer speed, reversibility, and specificity to inflammatory pathways. Here, we propose the concept of a “Chrono-PTM axis,” in which circadian timing and PTM-dependent signaling are functionally integrated to govern immune activation thresholds. We discuss how PTMs not only regulate core clock machinery but also temporally gate key innate immune pathways, including NF-κB signaling and inflammasome activation, thereby controlling cytokine production at multiple levels. Furthermore, we highlight the role of immunometabolism in supplying essential cofactors that couple cellular energetic states to PTM dynamics, linking metabolic oscillations to inflammatory outputs. Disruption of this axis contributes to the pathogenesis of autoimmune diseases, cancer, and tissue-specific inflammatory disorders. Finally, we outline emerging therapeutic opportunities targeting the Chrono-PTM axis, including chronotherapy and PTM-directed interventions, and identify critical gaps in temporal proteomics and translational studies. Elucidating the integration of circadian and post-translational regulation will provide a unifying framework for understanding immune homeostasis and may enable time-informed precision immunotherapy. Full article