Older adults remain highly vulnerable to severe SARS-CoV-2 outcomes despite multiple vaccinations, yet age-associated differences in immune responses to updated COVID-19 booster vaccines remain incompletely characterized. Here, we administered an XBB.1.5 trivalent recombinant protein booster (WSK-V102C) to 22 individuals (<38 years) and 20 individuals (≥73 years), all of whom had previously received 2-3 doses of inactivated COVID-19 vaccines. Neutralizing antibody responses against multiple SARS-CoV-2 variants were quantified and compared between age groups. Meanwhile, single-cell RNA sequencing was also performed on peripheral blood mononuclear cells (PBMCs) collected at baseline and 28 days post-vaccination to profile age-associated immune features following boosting. Following booster immunization, both age groups achieved significantly elevated antibody titers against all tested strains. Nevertheless, the magnitude of antibody fold increase was consistently lower in elderly individuals than in younger adults. Single-cell analyses revealed age-associated differences in post-vaccination immune organization. In elderly individuals, B-cell state transitions were characterized by transcriptional signatures consistent with memory B cell-to-plasmablast differentiation, whereas younger individuals predominantly exhibited transitions from naïve B cells. CD4+ T cells from elderly individuals displayed altered transcriptional trajectories and reduced T-cell receptor diversity relative to younger adults. In contrast, younger individuals showed coordinated B- and T-cell-associated transcriptional programs, including enrichment of transcription factors such as KLF7, CEBPB, CEBPD, and MAFB. Collectively, our study describes age-associated differences in immune coordination and cellular response patterns following XBB.1.5 booster vaccination. Further longitudinal and functional studies will be required to clarify the mechanistic basis and clinical implications of these observations.

This parallel randomised controlled trial examined the effect of a 4-week, high dose (Lf-High, 600mg/d) or low dose (Lf-Low, 200mg/d) oral lactoferrin (Lf) intervention versus placebo, on immune cell responses to respiratory virus, circulating immune cell subsets, and systemic inflammation. In healthy older adults (n=103, ≥50 years old), ex vivo cytokine release of interferon (IFN)-α2, IFN-γ, interleukin (IL)-6, and tumour necrosis factor (TNF)-α from isolated peripheral blood mononuclear cells (PBMCs) stimulated with rhinovirus A-16 (RV-16) or influenza A virus (H1N1), circulating immune cell subsets, and plasma IL-6, C-reactive protein (CRP) and TNF-α were assessed at baseline and 4 weeks. Ninety-seven participants completed the intervention (Lf-High n=32, Lf-Low n=31, placebo n=34, withdrawals n=6). There was no difference in RV-16 or H1N1-induced IFN-γ release between groups. At 4-weeks, RV-16-induced IL-6 was lower in Lf-High compared to placebo (P=0.001), and RV-16-induced IFN-α2 was higher in Lf-High compared to Lf-Low (P=0.04). Lf-High increased total T cells (P=0.03) and CD4+ T cells (P=0.03) compared to placebo. Lf-Low reduced neutrophil (P=0.04), natural killer cell (P=0.045), activated CD8+ T cell (P=0.03), and γδ T cell (P=0.03) frequency compared to placebo. Plasma IL-6 (P=0.004) and CRP (P=0.03) were lower following Lf-High compared to Lf-Low, but not placebo. Both high and low dose lactoferrin altered ex vivo immune cell responses after 4 weeks. High dose lactoferrin increased T-cell subsets, promoting adaptive immunity, and reduced systemic inflammation, while low dose lactoferrin reduced proinflammatory and cytotoxic immune cells. High and low dose lactoferrin supplements may have immunoceutical benefits in older adults.

Background Exposure to fine particulate matter (PM 2.5 ) increases asthma severity and reduces glucocorticoid responsiveness in children, yet the molecular mechanisms underlying PM 2.5 sensitivity remain unclear. We previously identified a PM 2.5 -sensitive asthma phenotype and developed a PM 2.5 sensitivity polygenic risk score (sPRS) correlated with asthma exacerbations and lung function decline. Research question We sought to determine whether genetic variants contributing to PM 2.5 sensitivity converge on specific biological pathways or transcriptional regulators, and whether children with a high sPRS exhibit immune transcriptional signatures consistent with heightened PM 2.5 susceptibility. Methods Genes implicated by sPRS variants were mapped using regulatory annotation tools and evaluated for pathway and transcription factor target enrichment. Peripheral blood mononuclear cells (PBMCs) from high- and low-sPRS children matched on long-term ambient PM 2.5 exposure were profiled using single-cell RNA sequencing. Donor-level pseudobulk differential expression was performed using a paired quasi-likelihood negative binomial framework, followed by exploratory pathway enrichment and perturbagen signature analyses. Results sPRS-implicated genes were enriched for transcriptional regulators linked to SMAD2/3- and MAPK-associated signaling, suggesting TGF-β1-related pathway involvement. No genes reached false-discovery-rate-adjusted significance at the donor level in this small, matched cohort. However, secondary pathway-level analyses demonstrated concordant enrichment across multiple immune populations in inflammatory and stress-response signaling programs previously linked to PM 2.5 exposure. Perturbagen signature analyses likewise highlighted small-molecule regulators of TGF-β1-associated pathways. Interpretation These integrative genomic and transcriptomic analyses nominate TGF-β1-SMAD/MAPK signaling as a biologically plausible axis of genetic susceptibility to PM 2.5 in pediatric asthma. Given the modest sample size and indirect nature of enrichment-based inference, these findings should be considered hypothesis-generating and motivate targeted functional validation.

Cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) is a critical cytosolic DNA sensor, whose activity can be regulated by acetylation. Here, we show that nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacetylase SIRT4 interacts with cGAS and positively regulates innate immune responses triggered by DNA viruses or cytoplasmic DNA. Overexpression of SIRT4 inhibits HSV-1 infection, whereas knockdown of SIRT4 has the opposite effect. Deficiency of SIRT4, or treatment with a SIRT4 inhibitor, impairs antiviral innate immune signaling in response to DNA viruses or cytoplasmic DNA, both in vitro and in vivo. Moreover, SIRT4 inhibitor treatment attenuates type I interferon signaling in Trex1-deficient cells and in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). Mechanistically, SIRT4 deacetylates cGAS and enhances its association with double‑stranded DNA. Collectively, our study identifies SIRT4 as a positive regulator of cGAS-mediated innate immune signaling pathways, which advances the understanding of the regulation of cGAS activity.

CD4 and CD8 T-cell lymphocytes from penile squamous cell carcinoma tumors are more differentiated with higher PD-1 expression compared to lymphocytes in peripheral circulation.

SGK1 downregulation co-occurs with leukocyte oligomeric α-synuclein accumulation in Parkinson's disease.

Objective To investigate the role and regulatory mechanism of monocytes in the dysfunction of vascular endothelial cell induced by Hantaan virus(HTNV) infection. Methods The in vitro co-culture model based on Transwell chambers was established [Human umbilical vein endothelial cells (HUVECs) were seeded in the middle layer, Human embryonic kidney cell 293 (HEK293) cells in the lower layer, and peripheral blood mononuclear cells(PBMCs) or monocyte-depleted PBMCs in the upper layer]. The monocytes in PBMCs were removed by the adherent method and the efficiency of removal was verified by flow cytometry (FCM). The expression of HTNV nucleocapsid protein (NP) in tissue cells was detected by Western blot to evaluate the effects of monocytes on viral replication. The levels of cytokine secretion and the states of T cell activation in the co-culture model were detected by Bio Plex suspension chip system and FCM, respectively. Finally, HUVEC permeability was assessed by measuring transepithelial electrical resistance (TER) following monocyte depletion or the addition of an anti-tumor necrosis factor α (TNF-α) neutralizing antibody. This was designed to determine whether monocytes exacerbate endothelial injury after HTNV infection by disrupting immune microenvironment homeostasis. Results Depletion of monocytes significantly increased HTNV NP expression in both HEK293 cells and HUVECs. Concurrently, levels of pro-inflammatory cytokines, including TNF-α, interleukin 1β(IL-1β), and IL-6, in the upper chamber culture medium were significantly reduced. Furthermore, the activation of cytotoxic T lymphocytes (CTL), type 1 helper T(Th1), Th2, and Th17 cells in the PBMCs was inhibited. The decline in the transepithelial electrical resistance of HUVEC was attenuated following monocyte removal, and this monocyte-mediated increase in endothelial permeability was reversed by the anti-TNF-α neutralizing antibody. Conclusion In this study, the methodology of the Transwell experiment is improved, allowing a better simulation of the in vivo process of HTNV infection. The findings reveal a dual regulatory role of monocytes in HTNV-induced vascular endothelial cell injury. Monocytes could not only inhibit HTNV replication but also promote T cell activation and increase vascular endothelial permeability through the secretion of pro-inflammatory cytokines such as TNF-α. Intervention targeting TNF-α significantly alleviate endothelial cell injury caused by HTNV infection.

IgG from anti-MDA5⁺ CADM patients impairs NK cell function via CD16 in RP-ILD.

Aging is a dominant risk factor for chronic diseases characterized by the functional decline of tissues and organs. During aging, the hematopoietic system declines in regenerative capacity-seemingly attributable to increases in DNA damage, replicative stress, and autophagic flux-resulting in skewing towards a myeloid lineage and away from a lymphoid lineage. Here, we characterized the transcriptomic and cellular landscape of the aged C57Bl/6J mouse hematopoietic system using a combination of bulk RNAseq and single cell RNAseq (scRNAseq). We show that aging leads to global transcriptional alterations in bulk peripheral blood mononuclear cells (PBMCs), lineage marker-depleted bone marrow cells (Lin-BM), and in hematopoietic stem and progenitor cells (HSPCs), immunophenotypically lineage marker negative (Lin-) Sca1+ cKit+ (LSK+). These changes indicate widespread activation of inflammatory processes, namely in PBMCs and Lin-BM cells. Interestingly, there is also a downregulation of cell cycle genes in HSPCs during aging. ScRNAseq across 39 hematopoietic cell types revealed age-related skewing in cell composition. Aged PBMCs showed significant decreases in CD4 and CD8 naïve cells concomitant with increases in CD4/8 memory and CD8 exhausted T cell populations. Lin-BM cells showed significant myeloid skewing in common myeloid progenitor (CMP) cells, as well as in the HSC population. We also identified a unique HSC population marked by increased Vwf, Wwtr1, and Clca3a1 expression that does not exist in young HSCs, thus likely marking true aged HSCs. Collectively, this work should serve as a useful resource for understanding and therapeutically targeting the aged hematopoietic system.

Mitochondrial function of peripheral lymphocytes: role on multiple sclerosis clinical subtypes.

Relationship between IL-17_A and pneumococcal carriage in children aged under two years: data from a randomised controlled trial in Vietnam.

Immunomodulatory and anti-proliferative effects of canine adipose-derived stromal vascular fraction on peripheral blood mononuclear cells: An in vitro model for therapeutic applications

Light-emitting anticancer Pt-cyclometalated phenanthroimidazole complexes.

Single-cell dissection of CD8+ T cell-driven immune dysregulation in type 1 diabetes mellitus: Mechanistic links to diabetic foot pathogenesis.

Temporal immune effects of Oral ketamine on PTSD: Transcriptomic evidence of short-term inflammation suppression and sustained immune Remodelling.

Butyrate ameliorates lung inflammation in chronic obstructive pulmonary disease in association with the regulation of histone lactylation: A mechanistic study.

Generation of the human iPSC line ESi148-A from a patient with sporadic amyotrophic lateral sclerosis.

Integrated transcriptomic and proteomic profiling identifies an interferon-dependent inflammatory endotype in sepsis.

Aberrant expression of microRNAs (miRNAs) has been closely linked to the progression of rheumatoid arthritis (RA). The present study explored the potential role of miR‑369‑3p in regulating immune‑driven inflammation and bone degradation in RA through the spectrin β, non‑erythrocytic 1 (SPTBN1)/Wnt/β‑catenin signaling cascade. To test this, synthetic mimics and inhibitors of miR‑369‑3p were generated and transfected into RA fibroblast‑like synoviocytes (RA‑FLSs). A pathological model was established by co‑culturing RA‑FLSs with peripheral blood mononuclear cells (PBMCs). The influence of miR‑369‑3p overexpression or suppression on RA‑FLS behavior was assessed in terms of cell survival, cell cycle distribution, proliferation and migratory capacity. Bioinformatics predictions together with luciferase reporter assays confirmed the direct interaction between miR‑369‑3p and SPTBN1. Expression levels of inflammatory cytokines, bone metabolism markers and matrix metalloproteinases were measured by ELISA, while reverse transcription‑quantitative PCR and western blotting were employed to evaluate alterations in the miR‑369‑3p/SPTBN1/Wnt/β‑catenin pathway. The results showed that miR‑369‑3p expression was markedly reduced in the PBMC‑induced RA‑FLS model. Transfection with miR‑369‑3p mimics suppressed the viability and proliferation of RA‑FLS and decreased the expression of SPTBN1, Wnt ligands and β‑catenin mRNA. By comparison, inhibition of miR‑369‑3p produced opposite effects. ELISA findings demonstrated that the miR‑369‑3p/SPTBN1 pathway modulated critical inflammatory and bone‑related markers, which were consistently confirmed across replicate experiments. These results suggested that miR‑369‑3p regulates RA pathology by targeting the SPTBN1/Wnt/β‑catenin pathway, attenuating inflammatory responses and limiting bone destruction in RA.

Generation of three induced pluripotent stem cell clones from a functional single ventricle patient carrying the BRAF c.1897T>C variant.