Journal of Immunology Research最新文献

Antiphospholipid syndrome (APS) is frequently coexisting with systemic lupus erythematosus (SLE) and the knowledge on its genetic background is essential. The objective of this work was to assess distribution of human leukocyte antigen (HLA)-DRB1 alleles in patients with APS with or without SLE in the context of Polish population data. The study was performed in a group of 112 patients with APS and healthy subjects to assess the distribution of HLA-DRB1 alleles in patients with APS and their association with clinical characteristics of patients with APS-antiphospholipid antibodies (aPLs) presence and disease activity/damage indexes. The distribution of HLA-DRB1 alleles showed significant differences between patients with APS and healthy subjects. Allelic variant HLA-DRB1⁣ ^∗ 1.15 was identified as risk alleles for APS observed in patients with APS (odds ratio (OR): 2.06 (1.27, 3.23), p=0, 004), while HLA-DRB1⁣ ^∗ 1.07 showed significant protective association (OR: 0.37 (0.14-0.76), p=0, 006). In subgroup of patients with coexisting SLE allelic variants above were not identified as risk or protective, while protective association was described for HLA-DRB1⁣ ^∗ 01, but not for patients in primary APS group. Presence of antibodies anti-β ₂-glycoprotein-I (aβ ₂GPI) IgA and against domain 1, anti-phosphatidylserine/prothrombin (aPS/PT) and anticardiolipin antibody (aCL) IgA all the antibodies which were negatively associated with HLA-DRB1⁣ ^∗ 15.01 carriers, what was reported for the first time may be suitable in discussion about value of these antibodies in practice and scientific research. This study clearly shows that primary APS has a distinct HLA-DRB1 associations as compared with SLE with a strong positive association with HLA-DRB1⁣ ^∗ 15.01 allele and a protective association with HLA-DRB1⁣ ^∗ 07.01.

Malaria is a parasitic infectious disease considered a public health problem. Acute respiratory distress syndrome (ARDS) is a complication in malaria-infected individuals with a high mortality rate (80% to 100%) and can occur before, during, or after antimalarial drug treatment. Although inflammation and epithelial/endothelial injury pathways have been determined through these studies, specific circulating malaria-associated ARDS markers have not yet been established. We applied a quantitative mass spectrometry (MS)-based proteomic approach to identify altered molecular pathways in a mouse model of malaria-associated ARDS. Acute-phase response (APR) proteins were regulated in the ARDS group, suggesting their potential involvement in the development of the syndrome. They may serve as biomarkers when analyzed alongside other proteins that require further investigation. Additionally, the regulation of APR proteins in the ARDS group provides valuable insights into the pathophysiology of ARDS, contributing to a better understanding of the syndrome.

Introduction: Tumor-infiltrating B cells (TILBs) are an important part of the immune response during tumor regulation. However, the significance of B cells in immunotherapy has not been fully determined. Methods: In this study, highly expressed genes in B cells were obtained by comparing the gene expression in B cells with that in other immune cells and were named TILB-mRNAs. Among them, those genes expressed in patients with head and neck squamous cell carcinoma (HNSCC) identified in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) atlas were employed to screen for genes associated with HNSCC prognosis using univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and a TILB-related signature was constructed to predict patient prognostic risk using multivariate Cox regression analyses. Results: The constructed TILB-related signature, which comprised seven mRNAs (ZNF439, KMO, KDM5D, IFT57, HDAC9, GSAP, and CCR7), was verified to have a good ability to predict the prognosis of patients with HNSCC using three independent validation datasets from GEO, and the predictive ability was not affected by other factors. The signature reflected the state of immune cell infiltration in tumor tissue, especially B cells, patients with higher risk scores (RSs) had fewer infiltrating immune cells in their tumors, especially B cells. The gene expression of the TILB-related signature was also verified in TILBs from HNSCC using single-cell analysis, revealing that TILB-related marker genes were differentially expressed in different GB cell subsets. Discussion: This study provides risk assessment and outcome prediction for patients with HNSCC and provides potential targets for immunotherapy of HNSCC.

Infections of central nervous system (ICNSs) are inflammatory diseases caused by infectious agents that can infiltrate the brain and spinal cord through various routes, including the bloodstream, peripheral nerves, or cranial nerves. Exosomes are found in plasma and have the capacity to cross the blood-brain barrier (BBB). Exosome constituents, including lipids, proteins, DNA, and RNA, change significantly over time and are correlated with the course of disease. Circular RNA (circRNA) has become a potential biomarker for various diseases, such as ICNSs. This study explores the diagnostic potential of circRNAs derived from brain-derived exosomes in ICNSs. Our research shows that the brain-derived exosomes from patients with CNS illnesses have different patterns of circRNA expression than those from healthy controls. Plasma samples from patients with bacterial ICNSs show significantly elevated levels of hsa_circ__0020840 and hsa_circ_0116108. In contrast, higher expression levels of hsa_circ_0056947 and hsa_circ_0021531 are observed in plasma samples from individuals with viral ICNSs compared to healthy subjects. These observations suggest their potential utility as sensitive and specific biomarkers for these diseases. Moreover, the capacity of circRNAs to be encapsulated within exosomes and released into circulation offers a noninvasive approach for diagnosing ICNSs. These findings highlight the promise of utilizing brain-derived exosomal circRNAs as novel diagnostic markers for ICNSs, which may have implications for improving patient outcomes and disease management.

In response to various stressors, cells can enter a state called cellular senescence which is characterized by irreversible cell cycle arrest and a senescence-associated secretory phenotype (SASP). The progressive accumulation of senescent glial cells in the central nervous system (CNS) with aging suggests a potential role for senescence as driver of aging and inflammation in the brain. As the main immune cell population residing in the CNS, microglia are thought to play a pivotal role in the progression of age-associated neuroinflammation. Furthermore, due to their slow turnover, microglia are highly susceptible to undergoing cellular senescence. However, current understanding of age-related changes in microglia and their impact on brain aging is limited. Due to the challenge in accessing human primary microglia and the lack of models to adequately recapitulate aging, this knowledge is predominantly limited to rodent studies. Here, we chemically induced senescence in a human immortalized microglia cell line with a cocktail of senescence-inducing molecules. We demonstrate that chemically induced senescent microglia adopt a proinflammatory phenotype, have reduced phagocytic activity, and impaired calcium activity. Our results show that chemically induced senescence can mimic features of cellular aging and can provide insight into the impact of aging and cellular senescence on human microglia.

Nucleated red blood cells (NRBCs) are precursors of red blood cells (RBCs), but also possess variety of immunomodulatory effects. However, among the three types of NRBCs, the immunological effects of human CD45- NRBCs remain largely unknown. We have previously shown that cord blood-derived CD45- NRBCs and adult peripheral blood-derived monocytes cocultured in a lipopolysaccharide (LPS)-stimulated indirect coculture system that avoided cell-to-cell contact, increase IL-10 and decrease TNF-α secretion, suggesting an immunosuppressive function of CD45- NRBCs via an unknown soluble factor. The peripheral blood of fetuses and neonates has abundant NRBCs and is physiologically polycythemic, which may lead to the peripheral accumulation of toxic plasma-free hemoglobin. Plasma-free hemoglobin binds to haptoglobin, forming a haptoglobin-hemoglobin complex, which is processed within monocytes via the CD163- heme oxygenase 1 (HO-1) axis and secretes IL-10. Therefore, we hypothesized that NRBCs secrete haptoglobin and induce the immunosuppressive function of monocytes by activating the CD163-HO-1 axis. We found that immunosuppressive response decreased when the coculture medium was supplemented with an anti-CD163 blocking antibody or the HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX). Haptoglobin levels in the culture medium containing NRBCs were high and expressed the haptoglobin gene. Thus, CD45- NRBCs secreted haptoglobin and activated the immunosuppressive function of monocytes.

Hepatic macrophages respond to various microenvironmental signals and play a central role in maintaining hepatic homeostasis, dysregulation of which leads to various liver diseases. Fatty acid-binding protein 7 (FABP7), an intracellular lipid chaperone for polyunsaturated fatty acids (PUFAs), is highly expressed in liver macrophages. However, the mechanisms by which FABP7 regulates hepatic macrophage activation remain unclear. Therefore, we aimed to elucidate the mechanisms underlying the effects of FABP7 on the functions of hepatic macrophages in metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis models. In this study, we found that FABP7-deficient macrophages exhibited impaired M2 polarization, which reduced the fibrotic response of myofibroblasts and CD4⁺ T-cell infiltration into the liver tissues in a carbon tetrachloride (CCl₄)-induced hepatic fibrosis model. In vitro, FABP7-deficient macrophages exhibited decreased levels of peroxisome proliferator-activated receptor (PPAR)-γ and its target genes, including C-C motif chemokine ligand (CCL)-17 and transforming growth factor-β (TGF-β), compared to the wild-type (WT) macrophages post-interleukin (IL)-4 stimulation. However, these effects were inhibited by a PPARγ inhibitor. IL-4-stimulated WT macrophages also promoted CD4⁺ T-cell migration and hepatic fibroblast (TWNT-1 hepatic stellate cell [HSC]) activation, indicated by increased mRNA levels of actin alpha 2, smooth muscle (ACTA2), and collagen type I alpha 1 (COL1A1); however, these effects were inhibited in FABP7-deficient macrophages. Overall, FABP7 in hepatic macrophages modulated the crosstalk between hepatic fibroblasts and T cells by regulating M2 polarization. Therefore, regulation of hepatic macrophage function by FABP7 is a potential therapeutic target for liver fibrosis.

Objectives: Primary Sjögren's syndrome (pSS) is associated with a risk allele T of rs117026326 located at a potential splicing enhancer within the intronic region of general transcription factor II-I (GTF2I). This study aimed to explore the rs117026326-regulated alternative splicing of GTF2I and its role in B cell overactivation in pSS. Methods: GTF2I isoform expressions and rs117026326 genotypes of pSS peripheral blood mononuclear cells (PBMCs) were examined using quantitative PCR and Sanger sequencing, respectively. GTF2IΔ was overexpressed in B cells, T cells, and macrophages using plasmid transfection. Proliferation of B cells and T cells was determined using Cell Counting Kit-8 (CCK8) assay. CD4⁺ T cell differentiation was inspected using flow cytometry. Proinflammatory cytokine production of macrophages was investigated using quantitative PCR. c-FOS expression in GTF2IΔ-transfected B cells was tested by quantitative PCR, and proliferation of GTF2IΔ-transfected B cells treated with c-FOS siRNA or c-FOS inhibitor was interrogated using CCK8 assay. Results: pSS patients with risk allele of rs117026326 expressed higher levels of GTF2IΔ and GTF2Iζ isoforms. GTF2IΔ expression was correlated with serum immunoglobulin G (IgG). GTF2IΔ promoted B cell proliferation and upregulated c-FOS expression. Knocking down or inhibition of c-FOS reversed B cell proliferation driven by GTF2IΔ. Conclusion: pSS risk allele of rs117026326 modulates alternative splicing of GTF2I and upregulates GTF2IΔ isoform, which promotes B cell proliferation through enhancing binding and transcription of c-FOS.

Research on long-term follow-up in individuals who have recovered from coronavirus disease-19 (COVID-19) would yield insights regarding their immunity status and identify those who need booster vaccinations. This study evaluated the longevity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular and humoral memory responses, as well as T cell effector functionalities, at 1-2 months (n = 40), 8-9 months (n = 40), and 12 months/1 year (n = 27) following recovery from SARS-CoV-2 infection. CTL response by enzyme-linked immunospot (ELISPOT); levels of cytokine by Bio-Plex, natural killer (NK), CD4+ helper, and CD8+ cytotoxic T cell functionalities using flow cytometry; anti-SARS-CoV-2 IgG by ELISA; and levels of neutralizing antibodies (NAbs) by surrogate virus NAb assay were assessed. The levels of SARS-CoV-2-specific IgG and NAb at 1-2 and 8-9 months postrecovery were hand in hand and appeared declining. SARS-CoV-2-specific B, memory B and plasma cells, and T cells sustained up to 8-9 months. Increased expression of CD107a/IFN-γ by NK cells and cytotoxic T cells at 8-9 months could be indicative of SARS-CoV-2-specific effector functions. Recovered individuals with positive and negative IgG antibody status displayed T cell response up to 1 year and 8-9 months, respectively, emphasizing the durabilty of effector immunity up to 8-9 months regardless of IgG antibody status. Overall, the recovered individuals exhibited robust immunological memory, sustained T cell response with effector functionality against SARS-CoV-2 that persists for at least 8-9 months.

Leishmaniasis is a group of parasitic diseases whose etiological agent is the protozoa Leishmania. These diseases afflict impoverished populations in tropical and subtropical regions and affect wild and domestic animals. Canine leishmaniasis is a global disease mostly caused by L. infantum. Dogs are recognized as a good reservoir since harbor the infection long before developing the disease, facilitating parasite transmission. Furthermore, there is growing evidence that dogs may also be the reservoir of the American Leishmania spp. as L. amazonensis. The innate immune response is the first defense line against pathogens, which includes natural killer (NK) and dendritic cells (DCs). By recognizing and ultimately destroying infected cells, and by secreting immune mediators that favor inflammatory microenvironments, NK cells take the lead in the infectious process. When interacting with Leishmania parasites, DCs become activated and play a key role in driving the host immune response. While activated DCs can modulate NK cell activity, Leishmania parasites can directly activate NK cells by interacting with innate immune receptors. Once activated, NK cells can engage in a bidirectional interplay with DCs. However, the complexity of these interactions during Leishmania infection makes it challenging to fully understand the underlying processes. To further explore this, the present study investigated the dynamic interplay established between monocyte-derived DCs (moDCs) and putative NK (pNK) cells of dogs during Leishmania infection. Findings indicate that the crosstalk between moDCs exposed to L. infantum or L. amazonensis and pNK cells enhances chemokine upregulation, potentially attracting other leukocytes to the site of infection. pNK cells activated by L. infantum infected DCs upregulate IL-10, which can lead to a regulatory immune response while moDCs exposed to L. amazonensis induced pNK cells to overexpress IFN-γ and IL-13, favoring a mix of pro- and anti-inflammatory response. In addition, parasite-derived extracellular vesicles (EVs) can modulate the host immune response by stimulating the upregulation of anti-inflammatory cytokines and perforin release, which may impact infection outcomes. Thus, Leishmania and parasitic EVs can influence the bidirectional interplay between canine NK cells and DCs.