Immune Molecules Research Articles

Age-dependent distribution of IgA and IgG antibody-secreting cells in the pharyngeal tonsil of the Bactrian camel.

The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.

Rapamycin Induces Phenotypic Alterations in Oral Cancer Cells That May Facilitate Antitumor T Cell Responses

Objectives: In this study, we investigated the antitumor immunomodulatory effects of rapamycin in oral cancer. Study Design: We examined the proliferation, apoptosis, and migration of cancer cells and investigated the cell surface expression levels of immune accessory molecules and T cell immune responses in vitro. We investigated the effect of in vivo administration of rapamycin on immune cell distribution and T cell immune responses in oral tumor-bearing mice. Results: Rapamycin treatment significantly inhibited OSCC cell proliferation and migration, increased apoptotic cell death, and upregulated cell surface expression of several immune accessory and adhesion molecules, including CD40, CD83, PD-L1, PD-L2, MHC class I, P-selectin, and VCAM-1. These cancer cells augmented T cell proliferation. In vivo rapamycin administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T cells, CD8+ T cells, and dendritic cells (DCs); decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor cells and regulatory T cells; enhanced DC maturation and upregulated the surface expression of CD40, CD86, and ICAM-1. Conclusions: Our results suggest that the therapeutic effect of mTOR inhibition in oral cancer can cause direct antitumor and immunomodulatory effects.

Breast Cancer Conditioned Media Modulate the Expression of Immune Checkpoints and Adhesion Molecules in Endothelial Cells

Breast Cancer Conditioned Media Modulate the Expression of Immune Checkpoints and Adhesion Molecules in Endothelial Cells

Fish novel TRIM protein FTR14 negatively regulates interferon response by targeting TBK1-IRF3

Growing evidence highlights that tripartite motif (TRIM) family members exert crucial functions in host defense upon infection with microbial pathogens. Of note, the roles of a subfamily of fish-specific TRIM (FTR, also named as finTRIM) which have no true orthologues in mammals were largely unexplored. In this study, a novel FTR gene from grouper (EcFTR14) was identified, and its effects on fish virus infection and host interferon response were investigated. EcFTR14 contained RING, B-Box, and PRY-SPRY domains, and shared 54.81% identity to zebrafish FTR14. The transcription levels of EcFTR14 were markedly induced upon fish virus infection. EcFTR14 was mainly localized in the cytoplasm as small spots or bright aggregates. The overexpression of EcFTR14 could markedly enhance the replication of RGNNV or SGIV. Moreover, overexpression of EcFTR14 reduced the mRNA level of IFN-associated immune signaling molecules, suggesting that the antiviral action of EcFTR14 was due to the negative regulation on IFN response. EcFTR14 was found to interact with EcTBK1, EcIRF3 and EcIRF7, but not with EcSTING. Overexpression of EcFTR14 markedly suppressed the transcription levels of IFN-signaling related molecules evoked by EcSTING and EcTBK1. In addition, overexpression of EcFTR14 could degrade EcTBK1, EcIRF3 and EcIRF7 in a dose-dependent manner, that resulted in the suppression of antiviral effects induced by EcIRF3 and EcTBK1. Collectively, our findings illuminated that EcFTR14, a novel member of FTR family, acted as a pro-viral factor through negatively regulating targeting TBK1-IRF3 activated antviral action. The present study will for the first time shed light on the regulatory roles of FTR14 in innate immune response upon fish virus infection.

Fam96a is essential for the host control of Toxoplasma gondii infection by fine-tuning macrophage polarization via an iron-dependent mechanism.

Toxoplasmosis affects a quarter of the world's population. Toxoplasma gondii (T.gondii) is an intracellular parasitic protozoa. Macrophages are necessary for proliferation and spread of T.gondii by regulating immunity and metabolism. Family with sequence similarity 96A (Fam96a; formally named Ciao2a) is an evolutionarily conserved protein that is highly expressed in macrophages, but whether it play a role in control of T. gondii infection is unknown. In this study, we utilized myeloid cell-specific knockout mice to test its role in anti-T. gondii immunity. The results showed that myeloid cell-specific deletion of Fam96a led to exacerbate both acute and chronic toxoplasmosis after exposure to T. gondii. This was related to a defectively reprogrammed polarization in Fam96a-deficient macrophages inhibited the induction of immune effector molecules, including iNOS, by suppressing interferon/STAT1 signaling. Fam96aregulated macrophage polarization process was in part dependent on its ability to fine-tuning intracellular iron (Fe) homeostasis in response to inflammatory stimuli. In addition, Fam96a regulated the mitochondrial oxidative phosphorylation or related events that involved in control of T. gondii. All these findings suggest that Fam96a ablation in macrophages disrupts iron homeostasis and inhibits immune effector molecules, which may aggravate both acute and chronic toxoplasmosis. It highlights that Fam96a may autonomously act as a critical gatekeeper of T. gondii control in macrophages.

Immunotherapies for food allergy: Exploring new targets and innovative strategies for enhanced efficacy

Food allergy is a growing public health concern. It affects children and adults, resulting in significant declines in the overall quality of life. In most cases, individuals must avoid consuming allergenic foods, which can be challenging, especially for patients who experience life-threatening symptoms even with minimal exposure to allergens. This review aimed to identify promising targets for immunotherapy in food allergy, strategies to reduce adverse reactions and side effects, optimal dosing approaches, clinical endpoints to measure efficacy, patient subgroups that benefit, and barriers to implementing immunotherapy. An in-depth literature review was conducted using PubMed and Google Scholar to look into novel approaches and possible targets for enhancing the effectiveness of immunotherapy. Targeting specific immune cells and molecules (e.g., IgE and Tregs), lowering the doses of allergens, extending intervals between doses, personalising dosing, selecting eligible patients carefully, and validating clinical endpoints have shown promising results in overcoming food allergy challenges and increasing immunotherapy efficacy. Potential innovative strategies to enhance immunotherapy efficacy encompass developing more cost-effective approaches, increasing access to trained specialists, developing standardised protocols, and collecting long-term data.

Genetic polymorphisms of TLR1, TLR2, TLR3 and TLR4 in patients with recurrent or severe infections.

Toll-like receptors (TLRs) play an important role in innate immunity. Previous studies have shown that single nucleotide polymorphisms (SNPs) in the genes coding for these innate immune molecules can affect susceptibility to and the outcome of certain diseases. The aim of the present study was to examine the clinical relevance of well-studied TLR1-4 SNPs in individuals who are prone to infections. Four functional SNPs, TLR1 rs5743618 (1805C>A, Ser602Ile), TLR2 rs5743708 (2258G>A, Arg753Gln), TLR3 rs3775291 (1234C>T, Leu412Phe) and TLR4 rs4986790 (896A>G, Asp299Gly), were analysed in 155 patients with recurrent respiratory infections (n=84), severe infections (n=15) or common variable immunodeficiency (n=56), and in 262 healthy controls, using the High Resolution Melting Analysis method. Polymorphisms of TLR2 rs5743708 (odds ratio [OR] 3.16; 95% confidence interval [CI] 1.45-6.83, p=.004, ap=.016) and TLR4 rs4986790 (OR 1.8; 95% CI 1.05-3.12, p=.028, ap=.112) were more frequent in patients with recurrent or severe infections than in controls. Interestingly, seven patients were found to carry both variant genotypes of TLR2 and TLR4, whereas none of the control group carried such genotypes (p≤.0001). Moreover, TLR2 polymorphism was associated with increased risk for acute otitis media episodes (OR, 3.02; 95% CI 1.41-6.47; p=.012). This study indicates that children and adults who are more prone to recurrent or severe respiratory infections carry one or both variant types of TLR2 and TLR4 more often than control subjects. Genetic variations of TLRs help explain why some children are more susceptible to respiratory infections.

Emerging evidence of context-dependent synapse elimination by phagocytes in the CNS.

Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions. The mechanism of synapse elimination by phagocytic glia is dependent on neuron-intrinsic factors, many innate immune and local apoptosis related molecules. During development, microglial synapse engulfment in the visual thalamus is primarily influenced by the classic complement pathway, whereas in the barrel cortex, the fractalkine pathway is dominant. In Alzheimer's disease, microglia employ complement-dependent mechanisms for synapse engulfment in tauopathy and early β-amyloid pathology. But microglia are not involved in synapse loss at late β-amyloid stages. Phagocytic microglia also engulfment synapses in complement dependent way in schizophrenia, anxiety and stress. Besides, phagocytic astrocytes engulf synapses in a MEGF10 dependent way during visual development, memory and stroke. Furthermore, the mechanism of a phenomenon that phagocytes selectively eliminating excitatory and inhibitory synapses is also emphasized in this review. We hypothesize that elucidating context-dependent synapse elimination by phagocytic microglia and astrocytes may reveal the molecular basis of synapse loss in neural disorders and provide a rationale for developing novel candidate therapies that target synapse loss and circuit homeostasis.

Spleen tyrosine kinase inhibitor R406 has both antiviral and anti-inflammatory effects on severe influenza A infection.

Death due to severe influenza is usually a fatal complication of a dysregulated immune response more than the acute virulence of an infectious agent. Although spleen tyrosine kinase (SYK) as a critical immune signaling molecule and therapeutic target plays roles in airway inflammation and acute lung injury, the role of SYK in influenza virus infection is not clear. Here, we investigated the antiviral and anti-inflammatory effects of SYK inhibitor R406 on influenza infection through a coculture model of human alveolar epithelial (A549) and macrophage (THP-1) cell lines and mouse model. The results showed that R406 treatment increased the viability of A549 and decreased the pathogenicity and mortality of lethal influenza virus in mice with influenza A infection, decreased levels of intracellular signaling molecules under the condition of inflammation during influenza virus infection. Combination therapy with oseltamivir further ameliorated histopathological damage in the lungs of mice and further delayed the initial time to death compared with R406 treatment alone. This study demonstrated that phosphorylation of SYK is involved in the pathogenesis of influenza, and R406 has antiviral and anti-inflammatory effects on the treatment of the disease, which may be realized through multiple pathways, including the already reported SYK/STAT/IFNs-mediated antiviral pathway, as well as TNF-α/SYK- and SYK/Akt-based immunomodulation pathway.

Clinical and Biologic Correlates of ADORA2A Transcriptomic Expression in Cancer.

ADORA2A (adenosine A2a receptor) and ADORA2B propagate immunoregulatory signals, including restricting both innate and adaptive immunity, though recent data also suggest a tumor suppressor effect in certain settings. We evaluated the RNA expression from 514 tumors in a clinical-grade laboratory; 489 patients with advanced/metastatic disease had clinical outcome correlates. Transcript expression was standardized to internal housekeeping genes and ranked (0-100 scale) relative to 735 specimens from 35 different cancer types. Transcript abundance rank values were defined as "low/moderate" (0-74) or "high" (75-100) percentile RNA expression ranks. Overall, 20.8% of tumors had high ADORA2A (≥75 percentile RNA rank). The greatest proportion of high ADORA2A expressors was found in neuroendocrine and breast cancers and sarcomas, whereas the lowest was found in colorectal and ovarian cancers, albeit with patient-to-patient variability. In multivariable logistic regression analysis, there was a significant positive correlation between high ADORA2A RNA expression and a high expression of the immune checkpoint-related molecules PD-1 (p = 0.015), VISTA (p ≤ 0.001), CD38 (p = 0.031), and CD39 (p ≤ 0.001). In 217 immunotherapy-treated patients, high ADORA2A did not correlate significantly with progression-free (p = 0.51) or overall survival (OS) (p = 0.09) from the initiation of the checkpoint blockade. However, high versus not-high ADORA2A transcript expression correlated with longer OS from the time of advanced/metastatic disease (N = 489 patients; (HR 0.69 (95% CI 0.51-0.95) (p = 0.02)). Therefore, high ADORA2A transcript levels may be a favorable prognostic factor, unrelated to immunotherapy. Importantly, ascertaining co-expression patterns of ADORA2A with PD-1 and VISTA in individual tumors as a basis for the precision co-targeting of ADORA2A and these other checkpoint-related molecules warrants investigation in clinical trials.

Structure-Based Rational and General Strategy for Stabilizing Single-Chain T-Cell Receptors to Enhance Affinity.

The T-cell receptor (TCR) is a crucial molecule in cellular immunity. The single-chain T-cell receptor (scTCR) is a potential format in TCR therapeutics because it eliminates the possibility of αβ-TCR mispairing. However, its poor stability and solubility impede the in vitro study and manufacturing of therapeutic applications. In this study, some conserved structural motifs are identified in variable domains regardless of germlines and species. Theoretical analysis helps to identify those unfavored factors and leads to a general strategy for stabilizing scTCRs by substituting residues at exact IMGT positions with beneficial propensities on the consensus sequence of germlines. Several representative scTCRs are displayed to achieve stability optimization and retain comparable binding affinities with the corresponding αβ-TCRs in the range of μM to pM. These results demonstrate that our strategies for scTCR engineering are capable of providing the affinity-enhanced and specificity-retained format, which are of great value in facilitating the development of TCR-related therapeutics.

Characterization, functional analysis, and expression of TNFR16 from Pinctada fucata martensii in response to exogenous stimuli and RNA interference

Marine pearls from Pinctada fucata martensii are valuable for decoration, skin care, and health care, but their quality and yield can be threatened by diseases, pearl nuclei transplantation rejection, and other external factors. The present study investigated the immune function of the tumor necrosis factor receptor (TNFR) gene in P. f. martensii to better understand immune responses related to nuclei rejection. The PmTNFR16 cDNA sequence obtained from cloning was 1675 bp in length and encoded 406 amino acid residues. Sequence analysis revealed that PmTNFR16 comprises one signal peptide domain, four TNFR domains, one transmembrane domain, and one death domain. Expression analysis revealed PmTNFR16 was highly expressed in the mantle and significantly up-regulated after exogenous stimuli. The effects of PmTNFR16 on immune effector molecules within the NF-κB signaling pathway were further explored using RNA interference probes for PmTNFR16. Pre-treatment of pearl oysters with dsRNA-PmTNFR before nucleus-insertion resulted in decreased expression of PmTNFR16 by 53 % at 24 h (p<0.01). Similarly, the expression of the NF-κB signaling pathway immune-related genes TRAF2, TRADD, IKK, NIK, and NF-κB significantly decreased at 24 h. The results indicated that PmTNFR16 was successfully silenced as were the expression of immune-related genes in the downstream NF-κB signaling pathway. Overall, these results indicate that PmTNFR16 may be involved in the immune response of the host organism by mediating the NF-κB signaling pathway. These observations provide a framework for future studies of the immune mechanisms of pearl oysters.

Maternal-Fetal Compatibility in Recurrent Pregnancy Loss.

Nowadays, recurrent pregnancy loss (RPL) is an undesirable condition suffered by many patients of reproductive age. In this scenario, certain immune cell populations and molecules, involved in maternal-fetal compatibility, have emerged as factors related with the pathogenesis of RPL. Among them, uterine Natural Killer cells (uNKs) appear to be of great relevance. These cells are involved in numerous processes during pregnancy, such as the remodeling of uterine spiral arteries or the control of trophoblast invasion. These functions are regulated by the interactions that these cells establish with the extravillous trophoblast, mainly through their Killer Immunoglobulin-like Receptors (KIRs) and the Human Leukocyte Antigen-C (HLA-C) molecules expressed by the embryo. A high level of polymorphism has been reported for both molecules involved in this interaction, with some of the possible KIR-HLA-C combinations being associated with an increased risk of RPL. However, the complexity of the maternal-fetal interface goes beyond this, as other HLA molecules also appear to be related to this reproductive pathology. In this review, we will discuss the role of uNKs in pregnancy, as well as the polymorphisms and clinical implications of KIR-HLA-C binding. We will also address the involvement of other, different HLA molecules in RPL, and the current advice on the appropriate management of patients with 'immunological mismatch', thus covering the main aspects regarding the involvement of maternal-fetal compatibility in RPL.

M6A-related bioinformatics analysis indicates that LRPPRC is an immune marker for ischemic stroke

Ischemic stroke (IS) is a common cerebrovascular disease whose pathogenesis involves a variety of immune molecules, immune channels and immune processes. 6-methyladenosine (m6A) modification regulates a variety of immune metabolic and immunopathological processes, but the role of m6A in IS is not yet understood. We downloaded the data set GSE58294 from the GEO database and screened for m6A-regulated differential expression genes. The RF algorithm was selected to screen the m6A key regulatory genes. Clinical prediction models were constructed and validated based on m6A key regulatory genes. IS patients were grouped according to the expression of m6A key regulatory genes, and immune markers of IS were identified based on immune infiltration characteristics and correlation. Finally, we performed functional enrichment, protein interaction network analysis and molecular prediction of the immune biomarkers. We identified a total of 7 differentially expressed genes in the dataset, namely METTL3, WTAP, YWHAG, TRA2A, YTHDF3, LRPPRC and HNRNPA2B1. The random forest algorithm indicated that all 7 genes were m6A key regulatory genes of IS, and the credibility of the above key regulatory genes was verified by constructing a clinical prediction model. Based on the expression of key regulatory genes, we divided IS patients into 2 groups. Based on the expression of the gene LRPPRC and the correlation of immune infiltration under different subgroups, LRPPRC was identified as an immune biomarker for IS. GO enrichment analyses indicate that LRPPRC is associated with a variety of cellular functions. Protein interaction network analysis and molecular prediction indicated that LRPPRC correlates with a variety of immune proteins, and LRPPRC may serve as a target for IS drug therapy. Our findings suggest that LRPPRC is an immune marker for IS. Further analysis based on LRPPRC could elucidate its role in the immune microenvironment of IS.

Prediction of immune molecules activity during burn wound healing among elderly patients: in-silico analyses-Experimental research

Introduction: Burn injuries lead to dysregulation of immune molecules, impacting cellular and humoral immune pathways. This study aims to determine the prediction of immune molecules activity during burn wound healing among elderly patients. Methods: The current study utilized the Gene Expression Omnibus (GEO) database to extract the proper gene set. Also, the literature review was conducted in the present study to find immune signatures. The study used the “enrich r” website to identify the biological functions of extracted genes. The critical gene modules related to mortality were identified using the weighted gene co-expression network analysis (WGCNA) R package. Results: The appreciated GSE was extracted. According to the data, the most upregulated signatures were related to Natural Killer (NK) Cells, and the most downregulated signatures were associated with M1 macrophages. Also, The results of WGCNA have shown that the most related gene modules (P&lt;107 and score 0.17) to mortality were investigated, and the modules 100 first genes were extracted. Additionally, the enrich r analysis has demonstrated related pathways, including; the immune process, including regulation of histamine secreted from mast cell (P&lt;0.05), T helper 17 cell differentiation (P&lt;0.05), and autophagy (P&lt;0.05) were obtained. Finally, by network analysis, the critical gene “B3GNT5” were obtained (degree&gt;ten and “betweenness and centrality”&gt;30 were considered). Conclusion: The study identified significant changes in macrophage and NK cell expression patterns post-burn injury, linking them to potential improvements in clinical outcomes and wound healing. The gene B3GNT5, associated with mortality, was highlighted as a key marker for prognostic evaluation.

The causes and consequences of trained immunity in myeloid cells.

Conventionally, immunity in humans has been classified as innate and adaptive, with the concept that only the latter type has an immunological memory/recall response against specific antigens or pathogens. Recently, a new concept of trained immunity (a.k.a. innate memory response) has emerged. According to this concept, innate immune cells can exhibit enhanced responsiveness to subsequent challenges, after initial stimulation with antigen/pathogen. Thus, trained immunity enables the innate immune cells to respond robustly and non-specifically through exposure or re-exposure to antigens/infections or vaccines, providing enhanced resistance to unrelated pathogens or reduced infection severity. For example, individuals vaccinated with BCG to protect against tuberculosis were also protected from malaria and SARS-CoV-2 infections. Epigenetic modifications such as histone acetylation and metabolic reprogramming (e.g. shift towards glycolysis) and their inter-linked regulations are the key factors underpinning the immune activation of trained cells. The integrated metabolic and epigenetic rewiring generates sufficient metabolic intermediates, which is crucial to meet the energy demand required to produce proinflammatory and antimicrobial responses by the trained cells. These factors also determine the efficacy and durability of trained immunity. Importantly, the signaling pathways and regulatory molecules of trained immunity can be harnessed as potential targets for developing novel intervention strategies, such as better vaccines and immunotherapies against infectious (e.g., sepsis) and non-infectious (e.g., cancer) diseases. However, aberrant inflammation caused by inappropriate onset of trained immunity can lead to severe autoimmune pathological consequences, (e.g., systemic sclerosis and granulomatosis). In this review, we provide an overview of conventional innate and adaptive immunity and summarize various mechanistic factors associated with the onset and regulation of trained immunity, focusing on immunologic, metabolic, and epigenetic changes in myeloid cells. This review underscores the transformative potential of trained immunity in immunology, paving the way for developing novel therapeutic strategies for various infectious and non-infectious diseases that leverage innate immune memory.

Exercise and osteoimmunology in bone remodeling.

Bones can form the scaffolding of the body, support the organism, coordinate somatic movements, and control mineral homeostasis and hematopoiesis. The immune system plays immune supervisory, defensive, and regulatory roles in the organism, which mainly consists of immune organs (spleen, bone marrow, tonsils, lymph nodes, etc.), immune cells (granulocytes, platelets, lymphocytes, etc.), and immune molecules (immune factors, interferons, interleukins, tumor necrosis factors, etc.). Bone and the immune system have long been considered two distinct fields of study, and the bone marrow, as a shared microenvironment between the bone and the immune system, closely links the two. Osteoimmunology organically combines bone and the immune system, elucidates the role of the immune system in bone, and creatively emphasizes its interdisciplinary characteristics and the function of immune cells and factors in maintaining bone homeostasis, providing new perspectives for skeletal-related field research. In recent years, bone immunology has gradually become a hot spot in the study of bone-related diseases. As a new branch of immunology, bone immunology emphasizes that the immune system can directly or indirectly affect bones through the RANKL/RANK/OPG signaling pathway, IL family, TNF-α, TGF-β, and IFN-γ. These effects are of great significance for understanding inflammatory bone loss caused by various autoimmune or infectious diseases. In addition, as an external environment that plays an important role in immunity and bone, this study pays attention to the role of exercise-mediated bone immunity in bone reconstruction.

Cutting edge of genetically modified pigs targeting complement activation for xenotransplantation.

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of xenotransplantation research. It begins by examining the mechanisms through which xenotransplantation activates both the classical and alternative complement pathways. It then assesses the current landscape of xenotransplantation from donor pigs, with a particular emphasis on the innovative strides made in genetically engineering pigs to evade complement system activation. These modifications are critical in mitigating the discordance between pig endogenous retroviruses and human immune molecules. Additionally, the review discusses pharmacological interventions designed to support transplantation. By exploring the intricate relationship between the complement system and xenotransplantation, this retrospective analysis not only underscores the scientific and clinical importance of this field but also sheds light on the potential pathways to overcoming one of the major barriers to the success of xenografts. As such, the insights offered here hold significant promise for advancing xenotransplantation from a research concept to a viable clinical reality.

In vitro immune analysis of serum from the hemolymph of the anomuran crab Albunea symmysta (Linnaeus, 1758) displayed diversified reactions

The present investigation aims to substantiate that serum from the hemolymph of anomuran crab Albunea symmysta encompasses multiple immunological reactions in in vitro condition. The serum highly agglutinated human O erythrocytes in the presence of Ba2+. Distinct and unique sugar binding capacity of serum towards laminarin, N-acetyl sugars and higher binding specificity towards a glycoprotein, fetuin was inferred. In vitro enhancement of melanin synthesis due to enhanced oxidation of 3, 4-dihydroxy-dl-phenylalanine (dl-DOPA) by preincubation of nonself molecules with serum phenoloxidase (PO) was documented. Similarly, dl-DOPA oxidation by serum PO was reduced when preincubated with chemical inhibitors and copper chelators. Further, the crab serum lysed the vertebrate erythrocytes with maximum hemolysis against chicken and it unveiled dependency on divalent cation, serum concentration, ionic strength, pH, temperature and time interval. Occurrence of maximum hemolysis at a concentration of 30 µl, pH 8.0, temperature 37 °C and time interval of 60 min in the presence of Ba2+ were documented. Interestingly, serum hemolysis was reduced by different osmoprotectants suggesting a colloid-osmotic mechanism involving in hemolysis. It was observed that A. symmysta serum had antimicrobial activity against Gram-positive Staphylococcus aureus and fungal pathogen Candida albicans. The serum showed higher glycan content, potent lysozyme and free radical scavenging activity suggesting the existence of potential immune molecules of therapeutic use. These results clearly demonstrated the diversified immunogenicity of A. symmysta serum confirming a highly conserved non-specific immunity of crustaceans

Antimicrobial peptide cecropin B functions in pathogen resistance of Mythimna separata.

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.