Shayo V, Nkinda L, Masoud SS
… +11 more, Mwendapole E, Thomas J, Kisuse J, Bwire G, Kibwana U, Majigo M, Kimaro JG, Mfinanga S, Senkoro M, Lyamuya E, Matee MI
Immunol Res
· 2025 Jun · PMID 40455126
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In July 2022, during the COVID-19 era, Tanzania reported over 1500 laboratory-confirmed measles cases and more than 30 deaths, with about 80% of the children not vaccinated. The response was an intensive vaccination camp...In July 2022, during the COVID-19 era, Tanzania reported over 1500 laboratory-confirmed measles cases and more than 30 deaths, with about 80% of the children not vaccinated. The response was an intensive vaccination campaign that targeted under-fives across the country. This was a cross-sectional measles-serosurveillance study conducted in 2024, after the COVID-19 era, in Dar es Salaam. The study involved children aged 3 to 15 years who were attending Temeke Regional Referral Hospital (TRRH) in Dar es Salaam, Tanzania, during the study period. Children were screened for anti-measles IgM and IgG antibodies using the NovaLisa Measles ELISA kit (NovaTec Immunodiagnostica GmbH® kit) and were categorized into four groups: (i) immune to measles (presence of anti-measles virus IgG and absence of anti-measles virus IgM), (ii) having reactivated measles (presence of both anti-measles virus IgG and anti-measles virus IgM), (iii) recently contracted measles (absence of anti-measles virus IgG and presence of IgM), and (iv) vulnerable (absence of both anti-measles virus IgG and anti-measles virus IgM). Of the 155 collected blood samples, 32 (20.64%) were positive for IgM, 35 (22.58%) cases were IgG-positive, and 74 (47.74%) had both IgM and IgG anti-measles antibodies. Based on these results, 35 (22.58%) children were determined to be immune, 74 (47.74%) were adjudged to have reactivated measles, 32 (20.64%) had recently contracted measles, and 14 (9.03%) were susceptible to measles infection. We found no significant association between gender, parents' education or income, frequency of facility visits, parents' knowledge of measles, and the presence of measles symptoms with IgM and IgG antibodies. The only significant association was age and IgM, being highest (22.58%) in children aged 3-5 years (P = 0.014), indicating risk of contracting measles in early childhood. This study provides an update regarding the current immunity status of children against measles infection in the post-COVID-19 era. Our study clearly indicates a need to improve measles immunization activities and strategies. The Government of Tanzania, through the Ministry of Health, should work together with international agencies such as the World Health Organization (WHO) and United Nations International Children's Emergency Fund (UNICEF) and other stakeholders to ramp up efforts to meet the target of 95% vaccination coverage.
Taherkhani A, Gorjizad M, Ahmadabadi F
… +9 more, Saberi M, Sharafian S, Mesdaghi M, Alavi S, Sayari AA, Abdolahzadeh S, Seraj S, Hassanipour H, Chavoshzadeh Z
Immunol Res
· 2025 May · PMID 40411647
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Stromal interaction molecule 1 (STIM1) is a transmembrane protein located in the endoplasmic and sarcoplasmic reticulum, where it plays a crucial role in activating calcium release-activated calcium (CRAC) channels. It f...Stromal interaction molecule 1 (STIM1) is a transmembrane protein located in the endoplasmic and sarcoplasmic reticulum, where it plays a crucial role in activating calcium release-activated calcium (CRAC) channels. It functions as a calcium (Ca⁺) sensor within the endoplasmic reticulum (ER), triggering CRAC channel opening and allowing calcium entry-mechanisms essential for maintaining intracellular calcium homeostasis. Mutations in the STIM1 gene that impair calcium signaling can disrupt both T cell and muscle cell function, leading to combined immunodeficiency and congenital myopathy. Here, we describe a 9-year-old boy with these clinical features, who was found to carry a previously undescribed mutation in the STIM1 gene. The patient presented with recurrent pneumonia, blood-streaked diarrhea, eczema, muscle weakness, and failure to thrive. Whole exome sequencing identified a novel homozygous missense variant in STIM1 (c.584T > C | p.Leu195Pro), considered likely pathogenic. This classification was supported by high Combined Annotation Dependent Depletion (CADD) and Rare Exome Variant Ensemble Learner (REVEL) scores of 29.8 and 0.89, respectively. Homozygosity of the mutation was confirmed using PCR-Sanger sequencing. This case highlights a novel homozygous STIM1 variant in a child with combined immunodeficiency and congenital myopathy. The clinical presentation is consistent with previously reported phenotypes associated with STIM1 deficiency.
Kaimwal A, Hadish M, Kumar A
… +2 more, Kumar A, Munshi A
Immunol Res
· 2025 May · PMID 40402330
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TRNA-derived fragments (tRFs) are tiny non-coding RNAs that control gene expression and immunological responses. Initially, the tRFs were thought to be only a byproduct of Transfer RNA (tRNA) degradation. Recent studies...TRNA-derived fragments (tRFs) are tiny non-coding RNAs that control gene expression and immunological responses. Initially, the tRFs were thought to be only a byproduct of Transfer RNA (tRNA) degradation. Recent studies highlighted their role in autoimmune diseases like type 1 diabetes (T1D), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The tRFs can influence the gene expression that are potentially involved in autoimmune diseases. The tRFs can alter immune cell function and influence the pathways that lead to autoimmune diseases. This review examines how tRFs impact immune system regulation, such as interactions with messenger RNAs (mRNA), inhibition of apoptosis, and immune cell development. Dysregulation of this leads to the progression or severity of autoimmune diseases. In addition, the potential of tRFs as biomarkers for autoimmune diseases and their targets of novel therapeutic interventions. However, this area is still in its infancy and needs more research to understand the role of a wide range of tRFs in autoimmune diseases.
Mehta S, Patel V, Agarwal S
… +3 more, Pant N, Suman S, Sohliya AEL
Immunol Res
· 2025 May · PMID 40397266
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Vitamin D is essential for regulating the immune system and preventing disease, yet vitamin D deficiency is common, especially in people living in polar regions. This systematic review examines the interplay between vita...Vitamin D is essential for regulating the immune system and preventing disease, yet vitamin D deficiency is common, especially in people living in polar regions. This systematic review examines the interplay between vitamin D levels, immune function, and the unique immunological challenges faced by polar residents. Through a comprehensive review of studies, three main areas were explored: (1) the impact of vitamin D deficiency on immune responses, (2) vitamin D status in polar regions, and (3) widespread immune deficiency in polar populations. Results showed that vitamin D deficiency is associated with increased vulnerability to respiratory infections, autoimmune diseases, and inflammatory diseases, while vitamin D supplementation consistently improved immune markers and downgraded disease severity. People living in polar regions face an increased risk due to limited solar radiation, diet, and environmental stressors, which contribute to increased immunosuppression, altered cytokine profiles, and susceptibility to infections. The summary findings highlight three key factors linking vitamin D deficiency, immune deficiencies, and unique health risks in polar populations. Addressing these deficiencies may be an effective strategy to strengthen immunity and reduce disease burden in these vulnerable groups.
Chen X, Shen B, Lin W
… +7 more, Xiong Z, Yang B, Luo H, Zong Z, Chen J, Bahabayi A, Liu C
Immunol Res
· 2025 May · PMID 40381105
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OBJECTIVE: This study aims to analyze CD27 expression in various subsets of CD4+ T cells in peripheral blood, explore the functional characteristics of the CD27+ subsets in regulatory T cells (Tregs) and CD4+ T cells, an...OBJECTIVE: This study aims to analyze CD27 expression in various subsets of CD4+ T cells in peripheral blood, explore the functional characteristics of the CD27+ subsets in regulatory T cells (Tregs) and CD4+ T cells, and assess their immunological alterations in newly diagnosed systemic lupus erythematosus (SLE) patients. METHODS: Peripheral blood was collected from 34 newly diagnosed, untreated SLE patients and 22 healthy controls. Flow cytometry was used to analyze CD27 expression on T cell subsets, comparing the functional markers between CD27+ and CD27- subsets. CD27 expression on Tregs and total CD4+ T cells in SLE patients and healthy controls were compared. ROC curves were constructed, and areas under the curve (AUCs) was calculated to evaluate the diagnostic value of CD27-related T cell subsets for SLE. RESULTS: The proportion of Tregs in the peripheral blood of SLE patients was increased, and CD27 expression was higher in Tregs than in CD4+ T cells in healthy individuals. CD27+ CD4+ T cells exhibited higher CD45RA and lower CD226 expression. CD27+ Tregs showed higher Helios and TIGIT expression and lower CD226 expression. CD27+ cell proportions in both CD4+ T cells and Tregs were significantly reduced in SLE patients. The AUC for CD27-related T cell subsets in diagnosing newly diagnosed SLE ranged from 0.6238 to 0.86. CONCLUSION: CD27 CD4 T cells show reduced activation features, while CD27 Tregs exhibit enhanced regulatory potential. Their decreased proportions in SLE patients suggest early immune dysregulation.
Firtina S, Saritas M, Ng YY
… +6 more, Nepesov S, Kiykim A, Bozkurt S, Bilgic-Eltan S, Ng OH, Sayitoglu M
Immunol Res
· 2025 May · PMID 40379838
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Severe combined immunodeficiency (SCID) represents a life-threatening inborn error of immunity, necessitating rapid diagnosis and intervention to prevent fatal outcomes. While SCID is characterized by profound T-cell lym...Severe combined immunodeficiency (SCID) represents a life-threatening inborn error of immunity, necessitating rapid diagnosis and intervention to prevent fatal outcomes. While SCID is characterized by profound T-cell lymphopenia, it may overlap with other conditions like ataxia-telangiectasia (AT), which also presents with T-cell deficiencies. This study examines two cases of suspected SCID in infants, later identified as AT due to pathogenic variants in the ATM gene. Despite initial negative results from SCID-targeted gene panels, further genetic testing revealed nonsense mutations (p.Y2036X and p.E1996X) in the FAT domain of the ATM gene, confirmed by Sanger sequencing. The patients exhibited significant T-cell lymphopenia and reduced ATM protein activity, indicative of AT. These findings highlight the importance of comprehensive genetic screening beyond common SCID-associated genes, especially in patients with atypical presentations. Early and accurate diagnosis can prevent mismanagement and guide appropriate therapies, improving patient outcomes.
Immunol Res
· 2025 May · PMID 40360944
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Psoriasis is a chronic autoimmune skin disorder characterized by keratinocyte hyperproliferation, inflammation, and angiogenesis, significantly impacting patients' quality of life. Current therapeutic strategies, includi...Psoriasis is a chronic autoimmune skin disorder characterized by keratinocyte hyperproliferation, inflammation, and angiogenesis, significantly impacting patients' quality of life. Current therapeutic strategies, including topical corticosteroids, phototherapy, and systemic biologics, often present limitations such as adverse effects, high costs, and inadequate skin penetration. Transdermal drug delivery offers a promising alternative by enhancing localized drug bioavailability and minimizing systemic side effects. In this study, we investigated the antipsoriatic potential of pemetrexed disodium, a multitargeted antifolate agent, formulated as a transdermal patch in an imiquimod-induced psoriasis mouse model. The patches were prepared using a solvent evaporation technique and optimized for controlled drug release. Mice treated with pemetrexed-loaded transdermal patches exhibited significant dose-dependent reductions in psoriasis severity, as evidenced by improvements in Psoriasis Area and Severity Index (PASI) scores, histopathological analysis, and suppression of inflammatory cytokines (TNF-α, IL-6) assessed via qRT-PCR and ELISA. The highest concentration (0.16 mg/cm) demonstrated the most pronounced therapeutic effects, comparable to the standard ketoconazole treatment. These findings highlight the potential of pemetrexed disodium-loaded transdermal patches as an innovative, targeted therapy for psoriasis, warranting further clinical investigations.
Immunol Res
· 2025 May · PMID 40358797
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Sepsis is a serious condition resulting from a dysregulated immune-mediated response to an infection. Myeloid-derived suppressor cells (MDSCs) aggregate and serve a protective function in the pathophysiology of lipopolys...Sepsis is a serious condition resulting from a dysregulated immune-mediated response to an infection. Myeloid-derived suppressor cells (MDSCs) aggregate and serve a protective function in the pathophysiology of lipopolysaccharide (LPS) shock. However, the regulation of MDSCs by chrysin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (CHR-NP) remains unexplored. CHR-NP was synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS). Before being given an intraperitoneal injection of 10 mg/kg of LPS, C57BL/6 mice were given CHR (50 mg/kg), PLGA (50 mg/kg), CHR-NP (50 mg/kg), and dexamethasone (Dexa) (5 mg/kg) by oral administration for 6 days. CHR-NP effectively mitigated LPS-induced splenic injury by diminishing inflammation and oxidative stress. The CHR-NP treatment lowered the amount of malondialdehyde (MDA) and raised the levels of antioxidants like glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx). Besides that, it stopped the production of cytokines that cause inflammation (tumor necrosis factor (TNF)-α, IL-1β, interferon (IFN)-γ, and IL-12) and increased the production of cytokines that stop inflammation (IL-10 and IL-4). This study demonstrates that CHR-NPs confer significant protective effects against LPS-induced sepsis by modulating immune responses, reducing oxidative stress, and alleviating splenic injury. The ability of CHR-NP to enhance antioxidant defenses, suppress pro-inflammatory cytokines, and promote anti-inflammatory mediators highlights its potential as a novel therapeutic approach for regulating MDSCs and mitigating sepsis-related immunopathology.
Carrillo-Vázquez DA, Balderas-Miranda JT, Rivera RIA
… +11 more, Pérez-Fragoso A, Alcalá-Carmona B, Nuñez-Aguirre M, Vargas-Castro AS, Absalón-Aguilar A, Lira-Luna J, Mejía-Domínguez NR, Juárez-Vega G, Anda KS, Torres-Ruiz J, Gómez-Martín D
Immunol Res
· 2025 May · PMID 40343598
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Anti-neutrophil extracellular traps (NETs) antibodies have been observed in patients with lupus nephritis and may contribute to the pathogenic role of NETs in patients with systemic lupus erythematosus (SLE). However, th...Anti-neutrophil extracellular traps (NETs) antibodies have been observed in patients with lupus nephritis and may contribute to the pathogenic role of NETs in patients with systemic lupus erythematosus (SLE). However, the prevalence of anti-NETs antibodies and their relationship with clinical features of patients with SLE have not been thoroughly studied, which is the aim of this study. Eighty-seven patients who fulfilled the 2019 EULAR/ACR Classification criteria for SLE were included. Plasmatic neutrophil elastase-DNA complexes as NETs remnants and the IgG anti-NETs antibodies were quantified by ELISA in the same sample. Thirty-one (35.6%) patients had positive anti-NETs antibodies. Patients with anti-NETs antibodies were younger at the time of recruitment (28.7 years (23.8-33.2) vs. 35.58 (27.88-45.77), p = 0.003) and had more prominent serological disease activity, with a higher prevalence of positive anti-double stranded (ds)-DNA antibodies (29 (93.5%) vs. 41 (73.2%), p = 0.022), higher titers (148.2 mg/dL vs. 35.6 mg/dL, p = 0.015), and lower levels of C3 and C4 (58 (37-85.5) vs. 77 (54-127), p = 0.017) and C4 (8 (8-12.5) vs. 20 (9-27), p < 0.001). From all clinical manifestations present at the time of recruitment, serositis showed a trend towards anti-NETs positivity (p 0.06). The global SLEDAI-2 K score was higher in the patient's IgG anti-NETs antibodies positive (13 (6.5-18) vs. 6 (4-15), p = 0.042). Anti-NETs antibodies were positively correlated with the systemic lupus erythematosus disease activity index (SLEDAI-2 K) score as well as with the titers of anti-dsDNA antibodies. IgG anti-NET antibodies were found in one-third of SLE patients. This is the first description of the association between IgG anti-NET and clinical features of SLE. Their characterization might allow us to address their role as potential novel biomarkers.
Salem Y, Yacov N, Kafri P
… +6 more, Propheta-Meiran O, Karni A, Maharshak N, Furer V, Elkayam O, Mendel I
Immunol Res
· 2025 May · PMID 40312574
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Monocytes are innate immune cells that drive the chronicity of various inflammatory diseases. Monocyte migration to inflamed tissues involves multiple steps of interaction with the vascular endothelium and the extracellu...Monocytes are innate immune cells that drive the chronicity of various inflammatory diseases. Monocyte migration to inflamed tissues involves multiple steps of interaction with the vascular endothelium and the extracellular matrix (ECM), a process mediated through conformational transitions in cell surface integrins. We previously described motile sperm domain-containing protein 2 (MOSPD2) as a surface protein expressed on myeloid cells that is essential for the migration of monocytes and a key regulator of inflammation. Investigating MOSPD2's mechanism of action, we assessed whether it plays a role in regulating integrin activation and monocyte adhesion. Data show that silencing of MOSPD2 expression in the THP-1 monocytic cell line significantly increased cell adhesion to various ECM molecules. Employing IW-601, a humanized anti-human MOSDP2 monoclonal antibody, on primary human monocytes increased adhesion to ECM molecules as well as to adhesion molecules. At the molecular level, silencing of MOSPD2 or blocking MOSPD2 using IW-601 led to a transition in integrin αLβ2 (CD11a/CD18, LFA-1) conformation into an active high-affinity binding form and to the induction of adhesion-associated signaling pathways. Co-immunoprecipitation experiments showed that MOSPD2 binds integrin-β2 (CD18), but not integrin-β1 (CD29). Our results reveal a novel mechanism controlling monocyte migration, in which MOSPD2 acts as an adhesion checkpoint that governs the balance between monocyte adhesion and release. By demonstrating the inhibitory effect of IW-601 on the migration of primary monocytes isolated from patients with chronic inflammatory diseases, we provide proof of concept for translating MOSPD2's mechanism into a potential treatment for inflammatory diseases, further supported by in vivo data in models of RA and IBD.
COVID- 19, which has affected millions of people across the globe as a pandemic, is caused by the SARS-Cov- 2 virus which has a case fatality rate of 2.3%. The clinical outcome of those who had mild and severe infection...COVID- 19, which has affected millions of people across the globe as a pandemic, is caused by the SARS-Cov- 2 virus which has a case fatality rate of 2.3%. The clinical outcome of those who had mild and severe infection exhibited different responses for the treatment due to differences in the host immune system. Predicting immune response with reliable biomarkers to monitor the severity and also identifying potential biomarkers that could help the clinician in decision-making would be important and also beneficial for the management of COVID- 19 in the hospital setup. In our study, we have used the NanoString nCounter gene expression assay to investigate the molecular signalling of host to COVID- 19 infection. The nCounter gene expression assay identified 29 genes that were differentially regulated and specific to COVID- 19 infection; out of which, 9 genes (ICAM3, PTAFR, CEACAM6, GBP1, C7, STAT1, CEACAM8, IL16, HLA-DPB1) exhibited strong predictive performance to differentiate COVID- 19 infection from healthy controls (AUC ≥ 0.9). We also observed that three genes (MAP4 K1, CTLA4, and HLA-DQB1) were able to differentiate COVID- 19 from patients with flu-like symptoms. A group of 11 genes (C2, CD14, CDKN1 A, CMKLR1, CYBB, HLA-A, IFNA2, LAG3, MARCO, TLR7, and IL15) showed a dysregulation trend with onset of COVID- 19 infection and settled to normal levels by day 14 as patient recovered. The outcome of our study may help in understanding the host immune response towards COVID- 19 infection.
Artificial intelligence (AI) has revolutionized various biomedical fields, particularly immunology, by enhancing vaccine development, immunotherapies, and allergy treatments. AI helps identify potential vaccine candidate...Artificial intelligence (AI) has revolutionized various biomedical fields, particularly immunology, by enhancing vaccine development, immunotherapies, and allergy treatments. AI helps identify potential vaccine candidates and predict how the body reacts to different antigens based on a vast number of genomic sequences and protein structures. AI can help cancer patients by analyzing their data and offering personalized immunotherapies. AI has also advanced the field of allergy by identifying potential allergens and predicting allergic reactions based on patient genetic and environmental factors. AI could also help diagnose multiple immunological diseases, including autoimmune diseases and immunodeficiencies, by analyzing patient history and laboratory results. AI has deepened our understanding of the human genome by providing numerous amounts of data from DNA sequences previously believed to be nonfunctional. Through machine learning and deep learning, many laborious research tasks, such as screening for DNA mutations, can be efficiently performed in a short amount of time. AI and machine learning are significantly advancing biomedical science in significant areas, including research and industry. This review discusses the latest AI-based tools that can be utilized in the field of immunology. AI tools significantly advance the field of medical research and healthcare by enabling new scientific discoveries and facilitating rapid clinical diagnosis.
Ischemic stroke (IS) has remained the main cause of mortality and neurological disabilities worldwide. Anti-CD20 treatments have a potent anti-inflammatory effect. Here, we investigated the effect of anti-CD20 on IS-indu...Ischemic stroke (IS) has remained the main cause of mortality and neurological disabilities worldwide. Anti-CD20 treatments have a potent anti-inflammatory effect. Here, we investigated the effect of anti-CD20 on IS-induced inflammation and histopathologic changes in the rat model. Male Sprague-Dawley rats were divided into three groups: control, sham, and stroke. Rats in the stroke groups underwent photothrombosis-induced IS in the sensorimotor cortex area. They were divided into the following subgroups: treated with anti-CD20 after ischemia and killed after 5 and/or 10 days of IS. Histological changes were assessed by hematoxylin and eosin staining. mRNA levels of inflammation markers (VIM, ANXA3, SLC22 A4, and ADM), and also levels of transcription factors for Th1, Th2, and Th17 subsets (Tbet, GATA3, and ROR-γ, respectively), and also Foxp3 were detected in the peripheral blood mononuclear cells by quantitative real-time PCR. The levels of ADM and SLC22 A4 increased following IS on the 5th and 10th days, while treatment with anti-CD20 reversed their levels. Anti-CD20 therapy attenuated inflammation through down-regulation of VIM and ANXA3 after 10 days. This therapeutic effect was mainly mediated by the downregulation of Th1-Th17-driven inflammatory responses (Tbet and RORγt) and the upregulation of Th2 activities (GATA- 3). In addition, anti-CD20 increased the expression of Foxp3. Anti-CD20 treatment can also reduce brain tissue damage after 10 days. Our data showed that inflammation and histopathological alterations are associated with the photothrombotic model of IS, while treatment with anti-CD20 could reduce inflammation and alleviate histopathological changes.
There is a strong association between Helicobacter pylori (H. pylori) and the occurrence of gastritis and gastric mucosal lymphoma in the human population. Vaccination is a viable preventive measure in light of the escal...There is a strong association between Helicobacter pylori (H. pylori) and the occurrence of gastritis and gastric mucosal lymphoma in the human population. Vaccination is a viable preventive measure in light of the escalating issue of antibiotic resistance. The use of DNA vaccines presents a potentially effective approach. This study used the utilization of antigenic H. pylori urease E subunit (UreE) for the development of a DNA vaccine. The UreE gene was chemically cloned into pIRES2-DsRed-Express (pDNA), and PCR and restriction enzyme digestion verified the cloning. The immunogenicity and immune-protective efficacy of the vaccination were assessed in BALB/c mice. In contrast, blood samples from BALB/c mice inoculated with pDNA-UreE showed higher levels of IgG, IFN-γ, IL- 4, and IL- 17. Furthermore, stomach damage and bacterial loads were reduced, and BALB/c mice inoculated with pDNA-UreE exhibited a significant protection rate (87.5%) against the H. pylori challenge. pDNA-UreE generated a combination of Th1-Th2-Th17 immune responses, perhaps contributing to adequate protection. Based on our findings, using this DNA immunization as a preventive measure against H. pylori infection is a viable approach.
A plethora of the cancer drugs with high therapeutic potential cannot pass the clinical trials because of their immunotoxic activities. In this study, we tested the immunomodulatory and immunostimulatory effects of the a...A plethora of the cancer drugs with high therapeutic potential cannot pass the clinical trials because of their immunotoxic activities. In this study, we tested the immunomodulatory and immunostimulatory effects of the anticancer agent alexidine dihydrochloride on J774.2 macrophage cell lines in vitro. The production levels of the pro-inflammatory cytokines (TNF-α, IL-6, GM-CSF, IL-12p40) were measured and compared by ELISA method. The activated (phosphorylated) JNK protein levels were measured by flow cytometer and the possible related intracellular signaling pathway was examined in this way. According to our results, alexidine dihydrochloride has an anti-inflammatory effect on the LPS-stimulated macrophage cell lines, as evidenced by reduced cytokine production compared to controls. Furthermore, its intracellular mechanism of action was found to be mediated partially through JNK signaling pathways. These findings suggest that alexidine dihydrochloride, while being an effective anticancer agent, may also modulate immune responses by dampening excessive inflammation. In this study, determining the anti-inflammatory effect of alexidine dihydrochloride on the immune system will seriously shed light on the role of this anticancer agent in future clinical studies and will provide a serious basis. In summary, the effects of the most drug-active ingredients on the inflammatory response in immune system cells have not been fully tested, and this creates the problem of many drugs failing in clinical studies or lack of knowledge on their side effects. Our study aimed to determine the effect of alexidine dihydrochloride, used as an anticancer agent, on the inflammatory response in J774.2 macrophage cell lines. Future studies with more immune system cells and a wider analysis of the intracellular signaling pathways will be informative about the immunotoxicity of the drug molecule. Future research involving a broader range of immune cell types and a more comprehensive analysis of intracellular signaling pathways will help clarify the immunotoxicity profile of this anticancer agent.
The major histocompatibility complex (MHC) encompasses a group of genes critical for immune system regulation. In humans, these molecules are referred to as human leukocyte antigens (HLA) due to their initial discovery i...The major histocompatibility complex (MHC) encompasses a group of genes critical for immune system regulation. In humans, these molecules are referred to as human leukocyte antigens (HLA) due to their initial discovery in human leukocytes. Class I molecules present antigens to CD8 + T cells, while Class II molecules present to CD4 + T cells. Here we report a patient who had a background of parental consanguinity and a family history suggestive of immunodeficiency. He presented with clinical symptoms including fever, septic arthritis, recurrent moniliasis. Preliminary diagnostic tests revealed hypogammaglobulinemia and CD4 lymphopenia. Further immunological assessment indicated extremely low expression levels of HLA molecules: HLA ABC at 5% and HLA DR at 0%. Genetic analysis showed a mutation in the regulatory factor X5 (RFX5) gene, leading to a combined immunodeficiency diagnosis. Consequently, hematopoietic stem cell transplantation (HSCT) was planned. Regulatory factor X5plays a pivotal role in immune function by transactivating genes critical for the expression of MHC Class I and Class II molecules, as well as beta- 2-microglobulin (B2M). MHC Class I transcription is controlled indirectly by RFX5, and the RFX5 gene mutation in the patient likely caused the markedly reduced expression of HLA ABC in addition to HLA DR. Combined HLA-ABC and HLA-DR expression analyses via flow cytometry may serve as a valuable diagnostic tool for identifying RFX5-related immunodeficiency at an early stage, facilitating timely genetic testing and appropriate clinical management.
Liu X, Luo A, Yang M
… +6 more, Luo J, Li H, Chen X, Mao B, Jiang H, Liu W
Immunol Res
· 2025 Apr · PMID 40234295
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Chronic obstructive pulmonary disease (COPD) is characterized by immune dysregulation, including altered innate lymphoid cell (ILC) immune responses, particularly during exacerbations (ECOPD). Baicalin, a natural compoun...Chronic obstructive pulmonary disease (COPD) is characterized by immune dysregulation, including altered innate lymphoid cell (ILC) immune responses, particularly during exacerbations (ECOPD). Baicalin, a natural compound prevalent in various herbal medicines, has shown promise as a therapeutic candidate in ECOPD. However, its potential and molecular mechanism for addressing ILC immune imbalance during ECOPD remain poorly understood. First, this study conducted a cross-sectional analysis of ILC immune responses in stable COPD patients and those experiencing exacerbations. Then, clinical findings of skewed ILC immunity were validated in cigarette smoke and lipopolysaccharide-induced ECOPD mouse models. Lastly, the therapeutic effect of baicalin on restoring ILC immune homeostasis was investigated in experimental ECOPD mouse models. Significant downregulation of ILC2 immunity was observed during COPD exacerbations, accompanied by increased ILC1 and ILC3 responses, particularly in cases associated with bacterial infections. Notably, elevated IL-22 levels were observed in this group. Administration of recombinant IL-22 in ECOPD mouse models disrupted lung ILC homeostasis, specifically inhibiting the accumulation of ILC2. Proteomics and transcriptomics analyses suggested IL-22 as a mediator of type 2 immune suppression by creating a molecular environment that favors type 1 and type 3 immunity. Treatment with baicalin effectively restored ILC2 immunity by enhancing the recruitment and activation of lung ILC2 while suppressing ILC1 and ILC3 responses. Importantly, baicalin attenuated IL-22 production from lung ILC3, highlighting its potential as an IL-22 inhibitor. Baicalin demonstrates potential as a therapeutic strategy for addressing ILC immune imbalance in COPD exacerbations, particularly by restoring ILC2 immunity and partially inhibiting IL-22 production. Clinical registration The cross-sectional study was registered with the Chinese Clinical Trial Registry (ChiCTR2100050683).
Accurate and accessible classification of anti-nuclear antibodies (ANA) through indirect immunofluorescence (IIF) imaging is crucial for diagnosing autoimmune diseases. However, many laboratories, particularly those with...Accurate and accessible classification of anti-nuclear antibodies (ANA) through indirect immunofluorescence (IIF) imaging is crucial for diagnosing autoimmune diseases. However, many laboratories, particularly those with limited resources, lack access to expensive commercial systems for automated analysis. This study evaluates the performance of an application developed by expert physicians using an artificial intelligence application (Microsoft Azure) to classify ANA IIF images. The results are compared with EuroPattern to assess the potential of AI in assisting laboratory experts, especially in resource-limited settings. A total of 648 ANA IIF images from the EuroPattern archive were used to train an AI model across nine classes with varying fluorescence intensities (+ to + + + +). Testing was conducted with 96 images, ensuring clarity by excluding mixed patterns. Microsoft Azure's Custom Vision service was employed for labeling and prediction. Expert evaluations, EuroPattern results, and AI classifications were compared. Both EuroPattern and the Azure-based AI model achieved 100% sensitivity, specificity, and accuracy in positive and negative discrimination. EuroPattern had an intraclass correlation coefficient (ICC) of 0.979, and the Azure-based AI model had an ICC of 0.948, indicating slightly lower performance. EuroPattern outperformed the Azure-based AI model in recognizing homogeneous, speckled, centromere, and dense fine-speckled patterns. The Azure-based AI model performed better in identifying cytoplasmic reticular/AMA-like patterns. The results suggest that AI-based image analysis tools, such as Azure, can be valuable for diagnostics in resource-limited labs. However, further testing with larger datasets and routine patient samples is needed to confirm their effectiveness in real-world clinical settings.
Immunol Res
· 2025 Apr · PMID 40199768
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HBV X protein (HBx), the smallest open reading frame in the hepatitis B virus (HBV) genome, can promote hepatocellular carcinoma (HCC) tumorigenesis by activating the expression of multiple oncogenes through inducing epi...HBV X protein (HBx), the smallest open reading frame in the hepatitis B virus (HBV) genome, can promote hepatocellular carcinoma (HCC) tumorigenesis by activating the expression of multiple oncogenes through inducing epigenetic alterations and interacting with the underlying transcriptional machinery. HBV non-infected HepG2 and Huh7 cells were transfected with HBx expression plasmids. The transcriptional, protein expression, and secretion levels of IGF-1 were detected by RT-qPCR, western blot, and ELISA, respectively. ChIP-qPCR was used to analyze the binding proteins on the IGF-1 gene. A co-culture system of HCC and Treg cells was designed using Transwell chambers. IGF-1 mRNA, protein, and secretion levels were increased in HepG2 and Huh7 cells exogenously expressing HBx. HBx was able to enter the nucleus and interact with the enhancer region of the IGF-1 gene. Levels of WDR5 and H3K4me1, which bind to the enhancer region of the IGF-1 gene, were also increased in HepG2 and Huh7 cells ectopically expressing HBx. Knockdown of WDR5 counteracted the upregulation of IGF-1 mRNA and protein levels by HBx. In the cell co-culture system, HBx/IGF-1 signaling in HCC cells promoted Treg cells expansion, IL-10 secretion, and infiltration, which was blocked by the IGF-1R inhibitor picropodophyllin. HBx/WDR5 promoted IGF-1 transcription in HCC cells through enhancers. HBx could promote Treg cell recruitment, infiltration, and activity by enhancing IGF-1 expression. IGF-1/IGF-1R signaling plays an important role in the communication between HCC cells and Treg cells. Targeting WDR or IGF-1/IGF-1R would be beneficial for the treatment of HCC.
Bullous pemphigoid (BP) is an autoimmune disease characterized by blister formation and inflammatory cell infiltration. In addition to eosinophil and neutrophil infiltration, there are many other inflammatory cells and f...Bullous pemphigoid (BP) is an autoimmune disease characterized by blister formation and inflammatory cell infiltration. In addition to eosinophil and neutrophil infiltration, there are many other inflammatory cells and factors involved in the pathophysiology of BP. Elucidating the inflammation environment will help to the diagnosis and treatment of BP. We used flow cytometry and wright-stained smears to analyze immune cells, and cytometric bead array methods were used to analyze immune factors in matched blood and blister fluid. Besides abundant eosinophil and neutrophil accumulation, distinct basophil infiltration was detected in blister fluid of patients with BP. We also found significant CD4 T lymphocyte activation and increased type 2 cytokine secretion in BP blister fluid. Under no stimulation, basophils produce more IL-4 compared to CD4 T lymphocytes in BP blister fluid. Basophils might play a more important role in BP than we early thought. Along with other inflammatory cells and factors, basophils, demonstrated as one of the main producers of IL-4, orchestrate the type 2 inflammation environment in BP.