Quantification of immunity is a challenge in clinical practice due to the complexity and heterogeneity of immune cells. This study aimed to establish comprehensive reference ranges for immune indicators and characterize immune heterogeneity in healthy adults. A total of 115 healthy adults aged 18-65 years were enrolled. Sixty immune indicators encompassing natural immunity (NK cells, monocytes, dendritic cells, myeloid-derived suppressor cells), cellular immunity (T cells, regulatory T cells, T follicular helper cells, T helper cells), and humoral immunity (B cells), along with nutritional and metabolic indicators, were simultaneously detected. Flow cytometry was used to measure the number, phenotype, and functional subsets of immune cells. Unsupervised k-means clustering was performed to identify immune subtypes. RNA-sequencing was conducted on representative individuals from each cluster for transcriptomic validation. The reference ranges for 60 immune indicators were established, with over half (38/60) exhibiting coefficient of variation > 30%, indicating substantial heterogeneity. Gender differences were minimal, whereas age-related changes were pronounced in adaptive immune cells. Specifically, human leukocyte antigen DR-positive (HLA-DR+) T cells (%) increased from 20.76% ± 7.75% (18-30 years) to 30.06% ± 10.82% (51-65 years, P = 0.001), while CD45RA+ regulatory T (Treg) cells (%) and naive CD8+ T cells (%) decreased progressively with age (P < 0.001). Correlation analysis between immune cells and routine laboratory indicators revealed that nutritional indicators like albumin (ALB) were positively correlated with the number of immune cells such as CD8+ T cells, while lipid metabolism indicators like low-density lipoprotein (LDL) were negatively correlated with T helper cell differentiation (P < 0.01). Clustering analysis identified three distinct immune subtypes: "potential type" (26.1%, n = 30) characterized by high naive T cells (44.91% ± 9.88% CD4+ T cells, 33.86% ± 13.82% CD8+ T cells) and CD1c-positive myeloid dendritic cells (CD1c+ mDCs) (45.17% ± 11.58%); "effector NK type" (34.8%, n = 45) with elevated NK cell count (704.22 ± 280.79 cells/μL) and cytotoxic function (93.16% ± 2.38% perforin+ NK cells); and "effector T type" (39.1%, n = 40) distinguished by increased HLA-DR+ T cells (19.48% ± 7.1% CD4+ T cells, 45.11% ± 10.92% CD8+ T cells) and effector memory (EM) CD4+ T cells (37.85% ± 11.01%). A further RNA-sequencing analysis confirmed the transcriptomic characteristics of different immune subtypes, which was in accordance with phenotype analysis. Specifically, adults in the potential type had strong adaptive immunity; those in the effector NK type showed upregulated NK cell-mediated cytotoxicity; those in the effector T type exhibited enhanced T-helper 1 immune responses. This study provides a systematic framework for immunity quantification by establishing reference ranges and classifying healthy adults into three immune subtypes with distinct metabolic and transcriptomic features. These findings could enhance understanding of immune heterogeneity in healthy individuals and guide personalized immune monitoring and intervention strategies in clinical practice.

Natural killer cells, macrophages and dendritic cells as innate immune therapies for blood cancers.

Elastin-like polypeptides (ELPs) are promising drug delivery vehicles, yet their bioactivities remain underexplored, likely due to the lack of applicable protein delivery systems. To address this, here, a fusion protein ELP19 (19.5 kDa) and a β-glucan nanogel (for short, BGNG) system were designed and constructed. The BGNGs formed using dual phenylboronic acid (PBA)-functionalized poly(ethylene glycol) as a cross-linker through a reverse microemulsion method were utilized to individually load two different ELP variants (another ELP with a molecular weight of 17.035 kDa, termed as ELP17) for intracellular delivery and bioactivity investigation. The synthesized BGNGs with a size of 77.9 nm exhibit excellent protein-loading and delivery capabilities, and the developed BGNG/ELP complexes retain excellent colloidal stability and cytocompatibility. In vitro studies reveal that the BGNG-mediated intracellular delivery of ELP19 significantly promotes macrophage polarization toward the M2 phenotype, whereas the delivery of ELP17 shows no such effect. In addition, the BGNG/ELP19 complexes are able to maturate dendritic cells to generate immunogenicity, while BGNG/ELP17 complexes do not have such immunogenicity. These findings highlight the functional divergence between the two different ELP variants and underscore the potential of BGNGs as a protein carrier and ELP19 as a modulator of macrophages, providing a reference for the future biomedical application of BGNG-based nanoplatforms and ELP-based therapeutics.

Hemorrhagic shock induces immune dysfunction via mesenteric lymph return, leading to systemic inflammatory response and multiple organ dysfunction. Dendritic cells (DCs) play a pivotal role in immune response following hemorrhagic shock. Therefore, identifying regulatory targets within DCs is essential for understanding hemorrhagic shock-induced immune dysfunction. Endoplasmic reticulum (ER) autophagy (ER-phagy), a selective form of autophagy, is critical for DC function. Here, we investigated the role of tumor necrosis factor-α-induced protein-8-like 2 (TIPE2), a protein known to regulate autophagy, in modulating DC ER-phagy after hemorrhagic shock. We analyzed the function and ER-phagy in splenic DCs from wild-type (WT) mice following hemorrhagic shock in vivo and DCs stimulated with posthemorrhagic shock mesenteric lymph (PHSML) in vitro . Our results showed an increased number of autophagosomes containing ER structures, with significantly enhanced colocalization between ER and autophagosomes in DCs during hemorrhagic shock. The proliferation of CD4 + T cells co-cultured with DCs was weakened, and the expression of surface molecules on the DCs was significantly increased after stimulation with PHSML. Subsequently, WT, TIPE2 -/- , and TIPE2 +/+ mice were used to further analyze the correlation between TIPE2 and ER-phagy in the context of hemorrhagic shock. The results demonstrated that under hemorrhagic shock conditions, TIPE2 -/- mice exhibited a significantly reduced microtubule-associated protein 1 light chain 3 (LC3)-II/I ratio and elevated SEC61 translocon subunit β (SEC61B) expression in the spleen tissue compared with WT mice, suggesting a diminished level of ER-phagy. Conversely, TIPE2 +/+ mice showed the opposite changes. Following stimulation with PHSML, the findings revealed a marked increase in the colocalization between ER and autophagosomes and a significant inhibition of DC function compared to the control group. Additionally, the deletion of TIPE2 weakened ER-phagy and decreased the inhibitory effect on DC function. In contrast, the overexpression of TIPE2 further enhanced ER-phagy and intensified the inhibition of DC function. In addition, TIPE2 is involved in the regulation of the nonclassical ER-phagy receptor tripartite motif 13 expression. These results suggest that ER-phagy is enhanced in DCs after hemorrhagic shock and that TIPE2 may regulate ER-phagy and DC function via tripartite motif 13. This research provides a theoretical basis for future clinical therapeutic strategies targeting the regulation of ER-phagy to improve the function of DCs.

MAP3K19 promotes the progression of hypopharyngeal cancer by suppressing dendritic cell maturation through mediating NF-κB activation and PD-L1 expression.

Oxidised 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC), dendritic cells (DCs), and long non-coding RNAs (lncRNAs) play crucial roles in atherosclerosis (AS). This study aimed to determine whether oxPAPC-induced DC-derived lncRNAs contribute to AS and to elucidate the underlying regulatory mechanisms. DCs were treated with increasing oxPAPC concentrations to assess transcriptomic changes. RNA sequencing was used to identify differential expression of lncRNAs. ChIP-Seq and RNA pull-down assays were used to assess direct binding between lncRNA CYP1B1-AS1 and NFATC2. The association between CYP1B1-AS1 and CYP1B1 was assessed using Pearson's correlation analysis. Elevated serum oxPAPC levels were confirmed in patients with coronary heart disease. Invitro, sustained oxPAPC stimulation activated the TLR4-MD2 pathway in DCs. CYP1B1-AS1 was identified as the key oxPAPC-induced DC-derived lncRNA, with Gm33055 as its murine homologue. RNA sequencing revealed oxPAPC-driven alterations in DC chemotaxis, differentiation, and lymphocyte activation. Analysis of human atherosclerotic plaque-derived DCs showed significant CYP1B1-AS1 upregulation. Gm33055 enhanced Cyp1b1 expression in murine DCs. Mechanistically, oxPAPC promoted NFATC2 nuclear translocation. NFATC2 binds to the CYP1B1-AS1 promoter, whereas CYP1B1-AS1 directly interacts with NFATC2, forming a positive regulatory loop. Adoptive transfer of m-CYP1B1-AS1-expressing DCs into Apoe-/- mice accelerated AS progression. These findings identify a DC-derived lncRNA-mediated regulatory axis that promotes AS and suggest potential therapeutic targets.

The Nrf2 activator tBHQ inhibits dendritic cell maturation and activation in response to bacterial and viral stimuli.

Lactiplantibacillus plantarum K4-9 strain stimulates antitumor immune responses through the activation of dendritic cells and CD8+ T cells.

Manipulation of tumor microenvironment by induction of immunogenic cell death and immune check point inhibitors for enhancing the efficacy of cancer treatments.

Altered CD163 and tweak expression in dendritic cells is associated with cardiac function post-acute myocardial infarction.

Spatial Single-cell Transcriptome Atlas of Mouse Thymus Reveals the T Lymphocyte Dynamics During Development.

Multiple sclerosis (MS) is a chronic autoimmune disease that leads to significant disability, with its precise etiology still not fully understood. Recent studies indicate the crucial role of immune cells in MS pathogenesis. However, traditional research often focuses on major immune cell populations, potentially neglecting the roles of newly identified immune cell subsets with distinct receptors and functions. Moreover, conventional observational studies are prone to biases, hindering the establishment of definitive causal relationships. This study aims to investigate the causal relationships between 731 immune cell traits and MS susceptibility using Mendelian randomization (MR) analysis to provide more robust insights into the underlying mechanisms of MS. We performed MR analyses to assess associations between various immune cell traits and MS risk. Following this, we explored the molecular mechanisms of the significant associations, focusing particularly on B-cell antigen presentation and the involvement of human leukocyte antigen (HLA) pathways. Our analysis revealed specific causal links between B cells and dendritic cells with MS susceptibility. We identified 61 pleiotropic genes associated with MS. Notably, B-cell antigen presentation and HLA-related pathways play pivotal roles in MS pathogenesis. Additionally, alterations in immune cell populations post-MS onset were observed, suggesting potential biomarkers for early diagnosis. This study offers a comprehensive examination of immune cell contributions to MS pathogenesis, identifying potential therapeutic targets and diagnostic markers. Given the side effects of anti-B cell monoclonal antibodies in MS treatment, our findings propose avenues for more precise therapeutic strategies aimed at minimizing adverse effects.

Virus like nanoparticles of VLP-BSA-iRGD enhanced mucosal immune response by targeting M cells.

High expression of a novel m6A reader LRPPRC predicts immunotherapy response and prognosis in head and neck cancer.

Major depressive disorder and Hashimoto's thyroiditis: Shared immunometabolic signatures revealed by integrative transcriptomics.

A multipronged Tα1 reset of CD8+ T cell cytotoxicity against breast cancer.

Endometrial immune profile: A predictor of pregnancy success.

Immunological response of using emulsifying elongation factor 1 alpha of Plasmodium falciparum-based vaccines in complete Freund's adjuvant.

Cellular landscape of reactive and neoplastic human lymph nodes in 3D.

Stereological quantification of tumor infiltrating immune cells as predictor of immunotherapy in metastatic melanoma.