Current research in immunology最新文献

Lymphoblastoid cell lines (LCLs) are immortalised peripheral B lymphocytes, transformed via infection with Epstein Barr virus (EBV). The use of LCLs to study B cell function remains controversial and core markers to define physiological B cell populations are not consistent between studies of physiological B cells and LCLs. A consensus on the nature of these commonly used cell lines has not been reached. Recently, a core set of markers to subtype peripheral B cells was proposed, addressing the lack of agreed markers for B cell characterisation. In this present study, the consensus panel was applied to describe the B cell subtypes in LCLs. We found that LCLs were generally not physiologically representative of B cells, with most cells harbouring marker combinations absent on peripheral B cells. Some B cell subtyping markers were fundamentally altered during EBV transformation to LCLs (e.g. CD19, CD21). Notably, most LCLs secreted IgG but the associated marker combinations were predominantly only present in vitro following EBV transformation. This study therefore informs interpretation of past investigations, and planning of future studies using LCLs, as these cells are unlikely to behave like their pre-transformed B cell subtype.

NK cells participate in ischemia reperfusion injury (IRI) and transplant rejection. Endogenous regulatory systems may exist to attenuate NK cell activation and cytotoxicity in IRI associated with kidney transplantation. A greater understanding of NK regulation will provide insights in transplant outcomes and could direct new therapeutic strategies. Kidney tubular epithelial cells (TECs) may negatively regulate NK cell activation by their surface expression of a complex family of C-type lectin-related proteins (Clrs). We have found that Clr-b and Clr-f were expressed by TECs. Clr-b was upregulated by inflammatory cytokines TNFα and IFNγ in vitro. Silencing of both Clr-b and Clr-f expression using siRNA resulted in increased NK cell killing of TECs compared to silencing of either Clr-b or Clr-f alone (p < 0.01) and when compared to control TECs (p < 0.001). NK cells treated in vitro with soluble Clr-b and Clr-f proteins reduced their capacity to kill TECs (p < 0.05). Hence, NK cell cytotoxicity can be inhibited by Clr proteins on the surface of TECs. Our study suggests a synergistic effect of Clr molecules in regulating NK cell function in renal cells and this may represent an important endogenous regulatory system to limit NK cell-mediated organ injury during inflammation.

Macrophages restrain microbial infection and reinstate tissue homeostasis. The mitochondria govern macrophage metabolism and serve as pivot in innate immunity, thus acting as immunometabolic regulon. Metabolic pathways produce electron flows that end up in mitochondrial electron transport chain (mtETC), made of super-complexes regulating multitude of molecular and biochemical processes. Cell-intrinsic and extrinsic factors influence mtETC structure and function, impacting several aspects of macrophage immunity. These factors provide the macrophages with alternate fuel sources and metabolites, critical to gain functional competence and overcoming pathogenic stress. Mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS) generated through the mtETC are important innate immune attributes, which help macrophages in mounting antibacterial responses. Recent studies have demonstrated the role of mtETC in governing mitochondrial dynamics and macrophage polarization (M1/M2). M1 macrophages are important for containing bacterial pathogens and M2 macrophages promote tissue repair and wound healing. Thus, mitochondrial bioenergetics and metabolism are intimately coupled with innate immunity. In this review, we have addressed mtETC function as innate rheostats that regulate macrophage reprogramming and innate immune responses. Advancement in this field encourages further exploration and provides potential novel macrophage-based therapeutic targets to control unsolicited inflammation.

Prostaglandin (PG)D₂ is produced and/or triggered by different parasites to modulate the course of the infection. These findings position PGD2 as a therapeutic target and suggest potential beneficial effects of repositioned drugs that target its synthesis or receptor engagement. However, recent in vivo data may suggest a more nuanced role and warrants further investigation of the role of PGD2 during the full course and complexity of parasitic infections.

Cytokines regulate periodontal pathogenesis and are relevant estimates of current disease activity. There is sparse information on status of cytokine protein levels in periodontal pocket (gingival) tissues. The current study analysed proteins and transcripts of selected cytokines in varying severity of periodontal disease and elucidated cytokine/cytokine ratios that best indicated periodontal disease severity, in gingival tissues. A total of 92 participants comprising of generalised moderate periodontitis (GMP, n = 18), generalised severe periodontitis (GSP, n = 46) and periodontally healthy controls (PHC, n = 25) were recruited for the study. Interproximal gingival tissue samples were utilised for cytokine protein estimation and mRNA quantification by qRT-PCR and ELISA respectively. Selected key pro and anti-inflammatory cytokines, also representative of various Th subsets were analysed. ROC curve analysis was performed and Youden index was calculated for individual cytokines and pro/anti-inflammatory cytokine ratio to estimate the best indicator of periodontal severity/progression in tissues. IL-1β, TGF-β and IFN-γ cytokine protein levels varied significantly (p ≤ 0.05) with severity of periodontal disease between groups. On comparison between deep and shallow sites within same participant, deep sites showed significant elevation of TGF-β (p ≤ 0.01) and IFN-γ (p ≤ 0.05) and IL-17 cytokines and shallow sites showed elevation of IL-4(p ≤ 0.01) and IL-1β (p ≤ 0.05) cytokines. Analysis of transcripts showed IFN-γ and IL-1β transcript predominance in GSP (p = 0.01) compared to PHC. ROC analysis illustrated 97% sensitivity, 93% specificity with Youden index of 90% for IL-1β cytokine and 81%sensitivity, 79% specificity with a Youden index of 60% for IL-1β/TGF-β ratio In periodontal pocket tissue, a lack of distinct predominance of specific cytokines between study groups or between shallow and deep sites affected by periodontal disease was observed. However, ROC analysis of cytokines revealed IL-1β cytokine and IL-1β/TGF-β ratio as promising indicators of periodontal disease severity in gingival tissues.

Malignant melanoma is a highly immunogenic tumour, and the immune profile significantly influences cancer development and response to immunotherapy. The peripheral immune profile may identify high risk patients. The current study showed reduced levels of CD4⁺ T cells and increased levels of CD8⁺ T cells in peripheral blood from malignant melanoma patients compared with controls. Percentages of peripheral CD56^dimCD16⁺ NK cells were reduced and CD56^brightCD16⁻KIR3⁺ NK cells were increased in malignant melanoma patients. Late stage malignant melanoma was correlated with low levels of CD4⁺ T cells and high levels of CD56^brightCD16⁻KIR3⁺ NK cells. Finally, high levels of Tregs in peripheral blood were correlated with poor overall survival and disease-free survival. The results indicate that changes in specific immune cell subsets in peripheral blood samples from patients at the time of diagnosis may be potential biomarkers for prognosis and survival. Further studies will enable clarification of independent roles in tumour pathogenesis.

RNA viruses always have been a serious concern for human health by causing several outbreaks, often pandemics. The excessive mortality and deaths associated with the outbreaks caused by these viruses were due to the excessive induction of pro-inflammatory cytokines leading to cytokine storm. Cytokines are important for cell-to-cell communication to maintain cell homeostasis. Disturbances of this homeostasis can lead to intricate chain reactions resulting in a massive release of cytokines. This could lead to a severe self-reinforcement of several feedback processes, which could eventually cause systemic harm, multiple organ failure, or death. Multiple inflammation-associated pathways were involved in the cytokine production and its regulation. Different RNA viruses induce these pathways through the interplay with their viral factors and host proteins and miRNAs regulating these pathways. This review will discuss the interplay of host proteins and miRNAs that can play an important role in the regulation of cytokine storm and the possible therapeutic potential of these molecules for the treatment and the challenges associated with the clinical translation.

The Semaphorin family is a group of proteins studied broadly for their functions in nervous systems. They consist of eight subfamilies ubiquitously expressed in vertebrates, invertebrates, and viruses and exist in membrane-bound or secreted forms. Emerging evidence indicates the relevance of semaphorins outside the nervous system, including angiogenesis, cardiogenesis, osteoclastogenesis, tumour progression, and, more recently, the immune system. This review provides a broad overview of current knowledge on the role of semaphorins in the immune system, particularly its involvement in inflammatory and infectious diseases, including chlamydial infections.

Inflammation is a general term for a wide variety of both physiological and pathophysiological processes in the body which primarily prevents the body from diseases and helps to remove dead tissues. It has a crucial part in the body immune system. Tissue damage can recruit inflammatory cells and cytokines and induce inflammation. Inflammation can be classified as acute, sub-acute, and chronic. If it remained unresolved and lasted for prolonged periods, it would be considered as chronic inflammation (CI), which consequently exacerbates tissue damage in different organs. CI is the main pathophysiological cause of many disorders such as obesity, diabetes, arthritis, myocardial infarction, and cancer. Thus, it is critical to investigate different mechanisms involved in CI to understand its processes and to find proper anti-inflammatory therapeutic approaches for it. Animal models are one of the most useful tools for study about different diseases and mechanisms in the body, and are important in pharmacological studies to find proper treatments. In this study, we discussed the various experimental animal models that have been used to recreate CI which can help us to enhance the understanding of CI mechanisms in human and contribute to the development of potent new therapies.

Introduction

Obesity is a pro-inflammatory disease critical for developing breast cancer (BC), which impacts the profiles of systemic inflammatory mediators and determinants of different disease clinical outcomes remains little explored.

Methods

A total of 195 patients diagnosed with breast cancer were included. Aiming to exclude chemotherapy interference on circulating mediators, samples were collected at diagnosis, out of the treatment period. Patients were classified as normal weight (BMI up to 24.9 kg/m2) or overweight (BMI ≥25.0 kg/m2). Serum levels of IL-4, IL-12, hydroperoxides, and nitric oxide metabolites (NOx) were measured. Also, tumor expression of inducible nitric oxide synthase (iNOS), TGF-β1, CD4⁺, and CD8⁺ lymphocytes were evaluated.

Results

IL-4 levels were significantly increased in the overweight BC group (p = 0.0329), including patients with luminal B subtype (p = 0.0443), presence of lymph node metastases (p = 0.0115) and age of diagnosis below 50 years, (p = 0.0488). IL-12 levels were significantly increased in overweight BC patients with lymph node metastases (p = 0.0115). Hydroperoxides were increased in overweight BC patients (p = 0.0437), including those with tumors smaller than 2 cm (p = 0.05). NOx levels were also increased in overweight BC patients, including those with luminal B disorders (p = 0.0443), high-grade tumors (p = 0.0351) and lymph node metastases (p = 0.0155). The expression of iNOS (p < 0.001) and TCD4+ lymphocytes (p = 0.0378) was significantly investigated in tumor biopsies from overweight BC women.

Conclusions

These data provide a picture of the influence of excess body weight on inflammatory mediators' systemic and tumoral profiles, especially in patients displaying poor outcome BC.