NKT Cells Research Articles

GIMAP1 interacts with TMX1 to improve lung adenocarcinoma prognosis by influencing tumor immune microenvironment.

Recent studies have indicated that the GIMAP family is downregulated in lung cancer and correlates with poor prognosis, although the underlying mechanisms remain unclear. This study aimed to elucidate the mechanism behind GIMAP1 downregulation in lung cancer. Bioinformatics tools were employed to assess the correlation between the GIMAP family and various cancers. Specifically, GIMAP1 was selected for further investigation, and its role in lung adenocarcinoma was confirmed through RNA sequencing analysis, Gene Set Enrichment Analysis (GSEA) of differentially expressed genes, correlation analysis with immune cell infiltration, and assay of the GIMAP1-TMX1 interaction. Based on bioinformatics analysis and real-world cohort studies, it was found that GIMAP1 was underexpressed in lung cancer tissues but exhibited elevated expression following immunotherapy. Overexpression of GIMAP1 was shown to influence several immune signaling pathways. In patients with high GIMAP1 expression, there was a significant increase in the infiltration of CD8+ T cells, activated memory CD4+ T cells, monocytes, and M1 macrophages; conversely, infiltration by M0 macrophages, resting dendritic cells (DCs), and plasma cells was significantly reduced. In vitro experiments showed that high levels of GIMAP1 increased the percentage of Treg, NK, and NKT cells. Additionally, GIMAP1 directly interacted with TMX1 and modulated the expression of downstream immune-related genes including CMTM5, IL17F, TRAV34, and XCR1. Therefore, GIMAP1 may serve as a promising therapeutic target in lung cancer, influencing both disease initiation and progression.

Lipid Antigens: Revealing the Hidden Players in Adaptive Immune Responses

Traditionally, research on the adaptive immune system has focused on protein antigens, but emerging evidence has underscored the essential role of lipid antigens in immune modulation. Lipid antigens are presented by CD1 molecules and activate invariant natural killer T (iNKT) cells and group 1 CD1-restricted T cells, whereby they impact immune responses to pathogens and tumors. Recent advances in mass spectrometry, imaging techniques, and lipidomics have revolutionized the identification and characterization of lipid antigens and enhanced our understanding of their structural diversity and functional significance. These advancements have paved the way for lipid-based vaccines and immunotherapies through the application of nanoparticles and synthetic lipid antigens designed to boost immune responses against cancers and infectious diseases. Lipid trafficking, CD1 molecule interactions, and the immune system’s response to lipid antigens are yet to be completely understood, particularly in the context of autoimmunity and microbial infections. In the years to come, continued research efforts are needed to uncover its underlying biological mechanisms and to exploit the full potential of therapies directed against lipid antigens.

Macrophages and Pulmonary Fibrosis.

Most chronic respiratory diseases often lead to the clinical manifestation of pulmonary fibrosis. Inflammation and immune disorders are widely recognized as primary contributors to the onset of pulmonary fibrosis. Given that macrophages are predominantly responsible for inflammation and immune disorders, in this review, we first focused on the role of different subpopulations of macrophages in the lung and discussed the crosstalk between macrophages and other immune cells, such as neutrophils, regulatory T cells, NKT cells, and B lymphocytes during pulmonary fibrogenesis. Subsequently, we analyzed the interaction between macrophages and fibroblasts as a possible new research direction. Finally, we proposed that exosomes, which function as a means of communication between macrophages and target cells to maintain cellular homeostasis, are a strategy for targeting lung drugs in the future. By comprehending the mechanisms underlying the interplay between macrophages and other lung cells, we aim to enhance our understanding of pulmonary fibrosis, leading to improved diagnostics, preventative measures, and the potential development of macrophage-based therapeutics.

Association of Healthy Eating Index (HEI)-2015 total and component scores with measures of inflammation and immune activation in healthy adults.

The Healthy Eating Index (HEI)-2015 measures diet quality and is associated with a lower risk of death from chronic disease. Dietary components may affect health via multiple mechanisms, including by decreasing inflammation and affecting immune activation. We hypothesized that the overall HEI-2015 score, or individual component scores, would be associated with altered inflammation and immune activation in healthy adults. The association of HEI-2015 scores with 88 inflammation and immune activation markers was examined in 346 adults without diagnosed disease using general linear models to adjust for covariates including visceral fat mass index (VFMI). The overall HEI-2015 score was inversely associated with plasma CRP and leukocyte concentrations, which are markers of inflammation, but these associations lost statistical significance with adjustment for VFMI. However, even with VFMI adjustment, the total vegetables score was inversely associated with total lymphocyte concentration (β = -0.157 ± 0.052, p = 0.019) and with monocyte and neutrophil activation (e.g., classic monocyte CD11b β = -0.153 ± 0.055, p = 0.030; neutrophil CD11b β = -0.122 ± 0.051, p = 0.049). The refined grain score was inversely associated with percent NK-T cells (β = -0.171 ± 0.058, p = 0.037), IL-10 production by T cells (β = -0.204 ± 0.057, p = 0.0039) and positively associated with plasma soluble CD14 (β = 0.220 ± 0.059, p = 0.0041). The total dairy score was positively associated with production of multiple cytokines by lipopolysaccharide-stimulated peripheral blood mononuclear cells (e.g., IL-1β β = 0.182 ± 0.054, p = 0.0066). Adjustment for VFMI decreased the association of HEI-2015 with inflammation, consistent with the known role of adiposity in mediating effects of poor diet on inflammation. This study also identified component scores associated with various aspects of immune activation that bear further study to clarify possible health benefits. ClinicalTrials.gov Identifier: NCT02367287.

The transcriptional profile of iron deficiency in patients with heart failure: Heme-sparing and reduced immune processes.

Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) and associated with morbidity and poor prognosis, but pathophysiological mechanisms are unknown. We aimed to identify novel biological pathways affected by ID. We studied 881 patients with HF from the BIOSTAT-CHF cohort. ID was defined as a transferrin saturation <20%. Transcriptome profiling was performed in whole blood. Identified targets were validated in a human in vitro stem cell-derived cardiomyocyte ID model utilizing deferoxamine as iron chelator. ID was identified in 554 (62.9%) patients, and 89 differentially expressed genes between ID and non-ID were identified, of which 60 were up- and 29 were downregulated. Upregulated genes were overrepresented in pathways of erythrocyte development and homeostasis. Heme biosynthetic processes were confirmed as relatively upregulated in ID, while iron-sulfur cluster assembly was downregulated. Downregulated processes further included natural killer cell and lymphocyte mediated immunity. In agreement with patient data, cardiomyocyte iron depletion significantly induced the expression of two genes (SIAH2 and CLIC4), which could be normalized upon iron supplementation. Both SIAH2 and CLIC4 are associated with increased mortality in patients with HF (hazard ratio 2.40, 95% confidence interval 1.86-3.11, p < 0.001 hazard ratio 1.78, 95% confidence interval 1.53-2.07, p < 0.001, respectively). Iron deficiency is associated with the preservation of heme-related processes at the cost of iron-sulfur clusters. Immune processes are downregulated, uncovering another high energy demand system affected. SIAH2 and CLIC4 might be modifiable factors in the relation between ID and impaired prognosis.

COVID-19 Serostatus Does Not Affect the Intrauterine Transfer of Micronutrients and Fatty Acids or Maternal–fetal Lymphocyte Cell Composition: An Observational Study

Objective Studies on the effects of coronavirus disease 2019 (COVID-19) on pregnant mothers and their newborns, specifically in relation to their micronutrient status, fatty acids (FAs), and inflammatory status are sparse. We hypothesized that COVID-19 infection would adversely affect the transfer of nutrients, and FAs from mothers to their fetuses via the umbilical cord and maternal–fetal distribution of inflammatory cells. This study aimed to determine the effect of COVID-19 on micronutrients, inflammatory markers, and FAs profiles in pregnant mothers and their newborns' cord blood. Study Design This was a cross-sectional study of 212 pregnant mothers in the third trimester and their newborns, recruited after testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serostatus. Peripheral blood of mothers and cord blood were collected at birth and analyzed for vitamin B12 (Vit B12), folic acid, 25(OH)D3, FAs, and peripheral blood mononuclear cells. Student's t-test or analysis of variance (ANOVA) was used to express statistical significance. Non-normal data were tested using the Mann–Whitney U test and Kruskal–Wallis test, with proportions compared with the chi-square test. Results Vit B12 levels were significantly low and adrenic acid levels significantly high in COVID-19 seropositive mothers while 25(OH)D3 was significantly low in seropositive cord blood. Irrespective of COVID-19 serostatus, folate, vit B12, saturated FA levels were significantly high in cord blood indicating their increased transfer from mothers to the fetus. However, monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA) levels were significantly lower in cord blood. Irrespective of COVID-19 serostatus, CD4+ T helper cells (percentage of lymphocytes) were significantly higher in cord blood, while NK cells, NK-T cells, and CD8+ T-cytotoxic cells—percentage of lymphocytes—were significantly lower in cord blood when compared with corresponding mother's blood. Conclusion The results indicate that while COVID-19 did not impede the transfer of essential nutrients such as MUFA and PUFA from mother to fetus, or affect maternal–fetal immune cell responses, it did appear to affect the levels of vit B12, vitamin D, and adrenic acid. Key Points

The α glycolipid rules the NKT cell TCR.

In this issue of JEM, Hosono et al. (https://doi.org/10.1084/jem.20240728) characterize a putative self- glycolipid that engages the iNKT cell TCR when bound to CD1d. The expression and distribution of this compound helps to explain some of the unusual properties of invariant NKT cells.

Can there be calm during a cytokine storm? Immune checkpoint pathways affecting the severity of COVID-19 disease

IntroductionThe COVID-19 pandemic has become a global health crisis, eliciting varying severity in infected individuals. This study aimed to explore the immune profiles between moderate and severe COVID-19 patients experiencing a cytokine storm and their association with mortality. This study highlights the role of PD-1/PD-L1 and the TIGIT/CD226/CD155/CD112 pathways in COVID-19 patients.MethodsWe performed a study using flow cytometry to compare the phenotypic and functional characteristics of peripheral blood mononuclear cells in patients with moderate or severe disease and healthy individuals. Soluble immune checkpoint molecule and ligand levels were measured by Luminex.ResultsSevere patients show reduced CD8+ T cell frequency, hyperactivation of CD8+ T, NK and NKT cells with concurrent upregulation of immune checkpoint ligands in monocytes. TIGIT expression by CD8+ T and NK cells and PD-1 by NKT cells suggest a spectrum of immune dysfunction, encompassing both hyperactivation and features of exhaustion. This dual phenomenon likely contributes to the impaired viral clearance and the exacerbation of inflammation characteristic of severe disease. Additionally, the study suggests that increased activation and cytotoxicity of NK cells may be associated with fatal outcomes in severe COVID-19 infection.ConclusionThese findings shed light on the intricate immune response regulation in COVID-19, emphasizing the importance of immune checkpoint pathways and activation signatures in disease severity. A novel aspect of this study is that it includes only COVID-19 patients experiencing cytokine storms, allowing for a focused analysis of immune dysregulation during this critical phase of the disease.

Understanding and Using Animal Models of Hepatotoxicity.

Hepatotoxicity is a critical health hazard, primarily contributing to the increased incidence of deaths globally. The liver is one of the major and extremely vital organs of the human body. Autoimmune diseases, viruses, exposure to toxicants such as carcinogens, and changes in eating habits can all cause liver problems, among other things. Free radical generation, together with raised enzyme levels including SGOT, SGPT, and total bilirubin, are among the pathological changes set off by liver injury. Hepatotoxicity causes changes in cells, such as eosinophilic cytoplasm, nuclear pyknosis, fatty degeneration, too many liver lesions, and hepatic centrilobular necrosis due to lipid peroxidation. Researchers have used animal models to investigate liver diseases and toxicities. Drugs such as azathioprine, alcoholism, paracetamol intoxication, and anti-tuberculosis drugs are some of the most common causes of liver toxicity. These toxins cause calcium ions (Ca2+), reactive oxygen species (ROS), and inflammatory mediators to be released inside cells. This activates immune cells like NK cells, NKT cells, and Kupffer cells. These signaling pathways also play roles in hepatotoxicity. Due to its pathogenesis, no effective drug is currently available for hepatotoxicity due to a lack of understanding related to the signaling factors involved in it. The paper primarily examines different experimental models of hepatotoxicity, including non-invasive and invasive methods, as well as genetic models. As such, these models are crucial tools in advancing our understanding of hepatotoxicity, thus paving the way for new therapeutic interventions.

Diverse immune cell profiles in ASFV-associated lymphopenia

Pathogenic African swine fever virus (ASFV) remains a lethal causative agent in the domestic pig industry, which poses a burden on the swine market and causes substantial socioeconomic losses worldwide. Currently, there are no commercially efficacious vaccines or specific treatments available for ASF prevention and control. Unfortunately, little is known about the swine immune response upon ASFV infection. Here, we investigated the host immune response discrepancy induced by the field moderately virulent strain ASFV HB-2208 among healthy, diseased and asymptomatic pigs. In the peripheral blood of diseased swine, lymphopenia is caused by the massive loss of bystander lymphocytes, such as γδ T cells, B cells and CD4+ T cells. Conversely, ASFV has a strong tropism for the mononuclear phagocyte system (MPS) and partial dendritic cells (DCs), whose antigen-presenting ability is impeded by the downregulation of CD80 and MHC I. However, no significant difference in the number of CD8αhigh T cells was detected, whereas the frequencies of NK cells, NKT cells, and regulatory T cells (Tregs) were significantly increased. Additionally, an in vitro model was established with a coculture of primary pulmonary alveolar macrophages (PAMs) and peripheral blood mononuclear cells (PBMCs), which significantly reduced γδ T cells, B cells and CD4+ T cells and increased Tregs. The differentiated immune response might aid in enhancing the understanding of ASFV pathogenesis in suids and provide insights into the mechanism of ASFV-induced lymphopenia for further studies.

Enhancing COVID-19 Vaccine Efficacy: Dual Adjuvant Strategies with TLR7/8 Agonists and Glycolipids.

The controlled release of immunostimulatory agents represents a promising strategy to enhance vaccine efficacy while minimizing side effects. This study aimed to improve the efficacy of the RBD-Fc-based COVID-19 vaccine through combining of an iNKT cell agonist and a TLR7/8 agonist using covalent conjugation and temporal delivery. We hypothesized that these combinations would yield a more balanced Th1/Th2 immune response. For covalent conjugation, we employed an uncleavable linker and a self-immolative disulfide linker to conjugate α-galactosylceramide (αGC) to imidazoquinoline (IMDQ). The αGC-SS-IMDQ-Ac conjugate, designed with a prodrug strategy for controlled TLR7/8 agonist release, elicited a higher IFN-γ/IL-4 T cell response ratio than individual adjuvants or their admixture. In the temporal delivery approach, administering IMDQ followed by αGC after 2 h resulted in the highest IgG2a/IgG1 ratio, significantly surpassing other groups. A 6 h delay between glycolipid and IMDQ injections yielded balanced IgG responses, enhancing IgG, IgG1, and IgG2a levels synergistically.

Large granular lymphocyte leukemia: a clonal disorder with autoimmune manifestations.

Large granular lymphocyte (LGL) leukemia is a rare lymphoproliferative disorder characterized by an expansion of clonal T or natural killer lymphocytes. Neutropenia-related infections and anemia represent the main manifestations. LGL leukemia is frequently associated with autoimmune disorders such as rheumatoid arthritis, Sjögren's syndrome, autoimmune endocrinopathies, vasculitis, or autoimmune cytopenia. Recent advances in the phenotypic and molecular characterization of LGL clones have underscored the pivotal role of a chronic antigenic stimulation and a dysregulation of the Jak/STAT signaling pathway in the pathophysiology linking leukemic-cell expansion and autoimmunity. In more than half of patients, there is a somatic STAT3 mutation. The disease is characterized by an indolent course, but approximately half of all patients will eventually require therapy. The first-line treatment for LGL leukemia is historically based on immunosuppressive agents (methotrexate, cyclophosphamide, or cyclosporine). However, cytokines blocking molecules or Jak/STAT inhibitors represent a new conceptual therapeutic approach for LGL leukemia. In this review, we present an overview of the spectrum of LGL proliferations, potential links between LGL expansion and autoimmunity, and therapeutic approaches.

Breaking the mold: Unconventional T cells in cancer therapy.

Unconventional Tcells, including invariant natural killer T (iNKT) cells, gamma delta (γδ) Tcells, and mucosal-associated invariant T (MAIT) cells, play important roles in both innate and adaptive immunity. These cells respond to tumors rapidly and influence the tumor microenvironment (TME). Recent advances in understanding their biology, as well as the development of novel therapeutic approaches, have underscored their potential in cancer immunotherapy. This commentary will assess these advances and translational possibilities in the field.

Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation.

Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post-cardiac arrest (CA) neurological injury. Here, we analyzed circulating immune cells from a large cohort of patients with OHCA, finding that lymphopenia independently associated with poor neurological outcomes. Single-cell RNA sequencing of immune cells showed that T cells with features of both innate T cells and natural killer (NK) cells were increased in patients with favorable neurological outcomes. We more specifically identified an early increase in circulating diverse NKT (dNKT) cells in a separate cohort of patients with OHCA who had good neurological outcomes. These cells harbored a diverse T cell receptor repertoire but were consistently specific for sulfatide antigen. In mice, we found that sulfatide-specific dNKT cells trafficked to the brain after CA and resuscitation. In the brains of mice lacking NKT cells (Cd1d-/-), we observed increased inflammatory chemokine and cytokine expression and accumulation of macrophages when compared with wild-type mice. Cd1d-/- mice also had increased neuronal injury, neurological dysfunction, and worse mortality after CA. To therapeutically enhance dNKT cell activity, we treated mice with sulfatide lipid after CA, showing that it improved neurological function. Together, these data show that sulfatide-specific dNKT cells are associated with good neurological outcomes after clinical OHCA and are neuroprotective in mice after CA. Strategies to enhance the number or function of dNKT cells may thus represent a treatment approach for CA.

Analysis of the Blood Levels of NK and NKT Cells in Patients with Severe SARS-CoV-2 Infection.

Clinical features of SARS-CoV-2 infection vary, ranging from asymptomatic cases to pneumonia, and other serious complications. Some populations have been observed to be at higher risk for severe disease and death compared to other ethnical groups. To evaluate two parameters of the innate immune system, that play a significant role in viral immunity. In samples of peripheral blood from sixteen patients with severe COVID-19, ten with asymptomatic to mild illness, and fifteen healthy subjects, the percentage of NK and NKT cells, the expression of different NK cell receptors and the blood levels of pro-inflammatory cytokines were tested. We observed that patients with severe COVID-19 showed significantly lower frequencies of both CD56dim and CD56bright NK cells compared to patients with mild illness or healthy controls. Furthermore, patients with severe manifestation of COVID-19 exhibited an aberrant expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46. Similarly, NK cells from these patients showed statistically significant differences in the expression of various killer immunoglobulin-like receptors (KIRs) in the two main cell subsets (CD56bright, CD56dim) compared to controls or patients with mild disease. Moreover, patients with severe illness displayed decreased frequency of NKT cells (defined as CD3+CD56+) and elevated blood levels of the cytokines IL-6 and IL-8. This study suggests that the abnormal features of NK and NKT cells observed in patients with severe SARS-CoV-2 infection may play an important role in the outcome of this infectious disease in various population groups.

Circulating immune landscape in melanoma patients undergoing anti-PD1 therapy reveals key immune features according to clinical response to treatment.

Immune checkpoint blockers (ICB) bring unprecedented clinical success, yet many patients endure immune mediated adverse effects and/or fail to respond. Predictive signatures of response to ICB and mechanisms of clinical efficacy or failure remain understudied. DC subsets, in network with conventional αβ T (Tconv), NK, γδ T and iNKT cells, harbor pivotal roles in tumor control, yet their involvement in response to ICB remained underexplored. We performed an extensive longitudinal monitoring of circulating immune cells from melanoma patients treated with first-line anti-PD1, before (T0) and during treatment. We assessed the phenotypic and functional features of DC and effector cells' subsets by multi-parametric flow cytometry and ProcartaPlex® dosages. We revealed differences according to response to treatment and modulations of patterns during treatment, highlighting a strong link between the immune landscape and the outcome of anti-PD1 therapy. Responders exhibited higher frequencies of circulating cDC1s, CD8+ T cells, and γδ2+ T cells in central memory (CM) stage. Notably, we observed a distinct remodeling of ICP expression profile, activation status and natural cytotoxicity receptor patterns of immune subsets during treatment. Anti-PD1 modulated DCs' functionality and triggered deep changes in the functional orientation of Tconv and γδT cells. Overall, our work provides new insights into the immunological landscape sustaining favorable clinical responses or resistance to first-line anti-PD1 therapy in melanoma patients. Such exploration participates in uncovering the mechanism of action of anti-PD1, discovering innovative predictive signatures of response, and paves the way to design pertinent combination strategies to improve patient clinical benefits in the future.

Development of a deep learning-based 1D convolutional neural network model for cross-species natural killer T cell identification using peripheral blood mononuclear cell single-cell RNA sequencing data

Background and Aim: Natural killer T (NKT) cells exhibit the traits of both T and NK cells. Although their roles have been well studied in humans and mice, limited knowledge is available regarding their roles in dogs and pigs, which serve as models for human immunology. Single-cell RNA sequencing (scRNA-Seq) can elucidate NKT cell functions. However, identifying cells in mixed populations, like peripheral blood mononuclear cells (PBMCs) is challenging using this technique. This study presented the application of one-dimensional convolutional neural network (1DCNN) for the identification of NKT cells within scRNA-seq data derived from PBMCs. Materials and Methods: We used human scRNA-Seq data to train a 1DCNN model for cross-species identification of NKT cells in canine and porcine PBMC datasets. K-means clustering was used to isolate human NKT cells for training the 1DCNN model. The trained model predicted NKT cell subpopulations in PBMCs from all species. We performed Differential gene expression and Gene Ontology (GO) enrichment analyses to assess shared gene functions across species. Results: We successfully trained the 1DCNN model on human scRNA-Seq data, achieving 99.3% accuracy, and successfully identified NKT cell candidates in human, canine, and porcine PBMC datasets using the model. Across species, these NKT cells shared 344 genes with significantly elevated expression (FDR ≤ 0.001). GO term enrichment analyses confirmed the association of these genes with the immunoactivity of NKT cells. Conclusion: This study developed a 1DCNN model for cross-species NKT cell identification and identified conserved immune function genes. The approach has broad implications for identifying other cell types in comparative immunology, and future studies are needed to validate these findings. Keywords: 1D convolutional neural network, K-means clustering, natural killer T cell, peripheral blood mononuclear cells, single-cell RNA sequencing.

IFN-γ-dependent regulation of intestinal epithelial homeostasis by NKT cells

Intestinal homeostasis is maintained through the combined functions of epithelial and immune cells that collaborate to preserve the integrity of the intestinal barrier. However, the mechanisms by which immune cell populations regulate intestinal epithelial cell (IEC) homeostasis remain unclear. Here, we use a multi-omics approach to study the immune-epithelial crosstalk and identify CD1d-restricted natural killer T (NKT) cells as key regulators of IEC biology. We find that NKT cells are abundant in the proximal small intestine and show hallmarks of activation at steady state. Subsequently, NKT cells regulate the survival and the transcriptional and cellular composition landscapes of IECs in intestinal organoids, through interferon-γ (IFN-γ) and interleukin-4 secretion. Invivo, lack of NKT cells results in an increase in IEC turnover, while NKT cell activation leads to IFN-γ-dependent epithelial apoptosis. Our findings propose NKT cells as potent producers of cytokines that contribute to the regulation of IEC homeostasis.

Effects of Psychological Stress on Multiple Sclerosis via HPA Axis-mediated Modulation of Natural Killer T Cell Activity.

The involvement of psychological stress and Natural Killer T (NKT) cells in the pathophysiology of multiple sclerosis has been identified in the progression of this disease. Psychological stress can impact disease occurrence, relapse, and severity through its effects on the Hypothalamic- Pituitary-Adrenal (HPA) axis and immune responses. NKT cells are believed to play a pivotal role in the pathogenesis of multiple sclerosis, with recent evidence suggesting their distinct functional alterations following activation of the HPA axis under conditions of psychological stress. This review summarizes the associations between psychological stress, NKT cells, and multiple sclerosis while discussing the potential mechanism for how NKT cells mediate the effects of psychological stress on this disease.

Analysis of the Potential Link Between Dermatomyositis and Cancer.

Dermatomyositis (DM) is an inflammatory muscle disease that increases the risk of cancer, although the precise connection is not fully understood. The aim of this study was to investigate the mechanisms linking DM to cancer and identify potential therapeutic targets. We conducted differential gene expression analysis on the GSE128470 dataset and employed WGCNA to pinpoint key genes related to DM. Central genes were identified with the LASSO and SVM-RFE methods. The expression levels and diagnostic relevance of these genes were confirmed via the GSE1551 dataset. Immune cell infiltration was analyzed in relation to central genes, and RT‒qPCR was utilized to evaluate the expression of key genes across various cancers. In total, differentially expressed genes (DEGs), involved mainly in innate immunity, cytokine responses, and autoimmune diseases, were identified. In the WGCNA, 399 significant genes related to DM were identified, with central genes including MIF, C1QA, and CDKN1A. Immune infiltration analysis revealed diverse immune cell populations in DM patients, with significant correlations between central genes and these immune cells. MIF levels were notably elevated in various tumors and correlated with the prognosis of specific cancers. Furthermore, MIF was negatively associated with most immune cells but positively correlated with CD4+ Th1 cells, NKT cells, and MDSCs. Factors such as immune regulatory elements, TMB, and MSI indicated that MIF may affect immunotherapy outcomes. The increased expression of MIF mRNA was confirmed via RT‒qPCR. The findings demonstrate that MIF, C1QA, and CDKN1A are differentially expressed in DM patients, with MIF showing significant alterations in DM patients with cancer. MIF may serve as a crucial prognostic biomarker and therapeutic target for various cancers, playing a pivotal role in linking DM to cancer through the modulation of CD4+ Th1 cells, NKT cells, and MDSCs.