Immunology[JOURNAL]
Sun
200 papers
Thyroid nodule and autoimmune thyroid disease frequency in adults with inborn errors of immunity: a case-control study.
Yarar Z, Gerek ME, Çölkesen F … +2 more , Arslan Ş, Karakurt F
BMC Immunol · 2026 May · PMID 42218402 · Full text
BACKGROUND: Inborn errors of immunity (IEIs) are defined by impaired immune function and abnormal immune system development. The recognition of significant interactions between the immune and endocrine systems has emerge...
BACKGROUND: Inborn errors of immunity (IEIs) are defined by impaired immune function and abnormal immune system development. The recognition of significant interactions between the immune and endocrine systems has emerged as an area of growing clinical interest. The study aimed to evaluate the frequency of thyroid nodules and autoimmune thyroid diseases in patients with IEIs. MATERIALS AND METHODS: This study included 40 IEI patients and 65 healthy subjects as control group. Demographic and clinical data were collected from medical records. All participants underwent thyroid ultrasound and biochemical evaluation for thyroid function tests and autoantibody levels. The diagnosis of autoimmune thyroid disease (AITD) diagnosis was based on thyroid specific autoantibody levels, thyroid function tests, and/or ultrasonographic features consistent with thyroiditis. RESULTS: Thyroid nodules were detected in 5 patients (12.5%) in the IEI group and in 14 subjects (21.5%) in the control group, with no statistically significant difference in thyroid nodule frequency between the two groups (p = 0.243). AITD was significantly more prevalent in the IEI group compared to controls (45.0% vs. 23.1%; p = 0.019). Mean total thyroid volume was significantly smaller in IEI patients than in controls (6.85 ± 2.92 mL vs. 10.52 ± 5.44 mL; p < 0.05). CONCLUSIONS: Our findings demonstrated that AITD is significantly more prevalent in IEI patients. Thyroid nodule frequency did not differ between groups. These findings support the routine incorporation of thyroid ultrasonography and autoantibody screening into IEI follow-up protocols. Larger multicenter prospective studies are warranted to confirm these observations across diverse IEI subtypes.
The LncRNA MIAT acts as a sponge for miR-942-5p to exacerbate the inflammation and oxidative stress in macrophages during sepsis-associated liver injury.
Shi J, Liu Z, Liu J … +1 more , Shi E
BMC Immunol · 2026 May · PMID 42218371 · Full text
BACKGROUND: Sepsis-associated liver injury (SALI) is a risk factor for high mortality in patients with sepsis. However, the pathological mechanism and treatment strategies of SALI remain unclear. This study aims to explo...
BACKGROUND: Sepsis-associated liver injury (SALI) is a risk factor for high mortality in patients with sepsis. However, the pathological mechanism and treatment strategies of SALI remain unclear. This study aims to explore the influence of lncRNA MIAT expression on SALI. RESULTS: The MIAT and TXNIP levels in the serum of SALI patients, RAW264.7 stimulated by LPS, and AML-12 co-cultured with RAW264.7 were increased, while miR-942-3p expression was decreased. The secretion level of inflammatory factors, the ROS positive rate, and the MDA content were increased, while the GSH levels and SOD enzymatic activity were reduced in LPS-stimulated RAW264.7. The activity of AML-12 was decreased, and the LDH level was increased. When the MIAT was inhibited, the above results showed opposite trends. MIAT was a molecular sponge for miR-942-5p and represses its activity. After inhibiting miR-942-5p, the inflammatory response and the oxidative stress level were enhanced in LPS-stimulated RAW264.7 and the damage of AML-12 was worsened. CONCLUSIONS: The silence of MIAT alleviated the inflammatory response and oxidative stress in LPS-induced RAW264.7 and alleviated the damage of AML-12 cells by adsorbing miR-942-5p.
Correlation analysis of positive Alzheimer's disease plasma biological markers with plasma immune cell and clinical characteristics in mild cognitive impairment patients in China.
Wang L, Zhang P, Gao S … +7 more , Liu H, Qiu X, Yang S, Wei L, Li Y, Cai Y, Yang J
BMC Immunol · 2026 May · PMID 42215876 · Full text
OBJECTIVE: The aim of the present work was to investigate the correlation between positive Alzheimer's disease (AD) plasma biological markers and plasma immune cell content as well as clinical characteristics in mild cog...
OBJECTIVE: The aim of the present work was to investigate the correlation between positive Alzheimer's disease (AD) plasma biological markers and plasma immune cell content as well as clinical characteristics in mild cognitive impairment (MCI) patients. METHODS: A total of 176 patients aged ≥ 65 years with MCI were followed up for two years. At baseline, AD plasma biomarkers (Aβ42, Aβ40, Aβ42/40, P-tau181 and PTau217) and immune cells (Treg cells, TH17 cells, lymphocytes) in MCI patients were detected, and their relevant clinical characteristics were recorded. Finally, the correlation between positive AD plasma biomarkers and immune cells, relevant clinical characteristics of MCI patients, and whether they would progress was analyzed. RESULTS: Plasma Aβ42/40 levels are negatively correlated with age, a history of hypertension, constipation symptoms, and the TGF-β/Treg cell ratio. They are positively correlated with the TIM3+/Treg cell ratio, the number of CD19-positive cells, the CD4/CD8 ratio, and the number of CD8-positive cells. Plasma PTau217 levels are positively correlated with age, the proportion of B cells, and the proportion of NK cells, and negatively correlated with visual-spatial executive function and attention cognitive domain scores. Dual abnormalities of Aβ42/40 and PTau217 are positively correlated with age and the proportion of B cells, and negatively correlated with cognitive domain scores for executive ability, attention, and language ability. CONCLUSION: Abnormalities in AD plasma biomarkers are associated with immune activation (particularly B cells and NK cells), aging, cardiovascular and gastrointestinal risk factors, and cognitive decline. The concurrent abnormalities of multiple biomarkers may exacerbate these associations, although some immune regulatory pathways do not show significant effects.
Why pigs might help us develop better vaccines and drugs against influenza virus.
Driver JP, Rajao DS, Singanayagam A … +2 more , Torremorell M, Tchilian E
Nat Rev Immunol · 2026 Jul · PMID 42215710 · Publisher ↗
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Eosinophils shape barrier immunity during reproduction.
Flemming A
Nat Rev Immunol · 2026 Jul · PMID 42215709 · Publisher ↗
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Neutrophil Secretory Proteins Inhibit Calcium Oxalate Crystallisation and Crystal Growth, but Promote Crystal Aggregation.
Lertprapai C, Peerapen P, Thongboonkerd V
Immunology · 2026 May · PMID 42210560 · Publisher ↗
Neutrophil secretory proteins are frequently found in calcium oxalate (CaOx) kidney stone matrix, suggesting their involvement in stone pathogenesis, but with unclear mechanisms. We therefore investigated the effects of...
Neutrophil secretory proteins are frequently found in calcium oxalate (CaOx) kidney stone matrix, suggesting their involvement in stone pathogenesis, but with unclear mechanisms. We therefore investigated the effects of secretome (a set of secretory proteins) from CaOx monohydrate (COM)-exposed versus control dHL-60 (neutrophil-like) cells on crystal nucleation (crystallisation), growth, aggregation and invasion. Quantitative proteomics was also performed to identify significantly altered secretory proteins, followed by analyses of their physicochemical properties and biological relevance. The data demonstrated that both COM-treated and control secretomes inhibited crystallisation and crystal growth, but the inhibitory effects from the COM-treated secretome were slightly weaker. By contrast, both of them promoted crystal aggregation, with the more potent effect from the COM-treated secretome. However, neither of them had a modulatory effect on crystal invasion. Quantitative proteomics revealed 20 decreased and 9 increased proteins in the COM-treated secretome compared with the control. Analyses of physicochemical properties showed that the increased secretory proteins tended to have a lower instability index and a smaller number of oxalate-binding motifs/protein. Main molecular functions of the increased group were catalytic, hydrolase and transporter activities, whereas those of the decreased group included RNA binding, molecular adaptor activity and catalytic activity. These data indicate that the neutrophil secretome inhibits crystallisation and crystal growth but promotes crystal aggregation. The COM-treated secretome exerts weaker inhibitory effects on crystallisation and growth but has a stronger promoting effect on crystal aggregation. These findings enhance our understanding of the roles of neutrophils in kidney stone pathogenesis.
Clinical role of miR-1271-5p in severe pediatric pneumonia and its prognostic value.
Chen J, Wang L
BMC Immunol · 2026 May · PMID 42210083 · Full text
BACKGROUND: As a predominant driver of pediatric mortality, severe pediatric pneumonia (SPP) is an important complication to be solved. The miR-1271-5p is universally engaged in pulmonary infection. This study focused on...
BACKGROUND: As a predominant driver of pediatric mortality, severe pediatric pneumonia (SPP) is an important complication to be solved. The miR-1271-5p is universally engaged in pulmonary infection. This study focused on miR-1271-5p for the first time and aimed to reveal its role in SPP. METHODS: The study enrolled 268 children aged 2-10 years, comprising 81 healthy individuals and 187 with pneumonia. The expression level of serum miR-1271-5p was assessed by qRT-PCR. The receiver characteristic (ROC) curve was employed to distinguish pneumonia children from healthy controls. Multivariate logistic regression analyzed factors associated with progression from mild-moderate pneumonia to SPP. Multivariate Cox regression assessed the association of miR-1271-5p expression with poor prognosis, and the Kaplan-Meier survival curve was subsequently generated based on miR-1271-5p levels. RESULTS: Serum miR-1271-5p levels were remarkably elevated in children with pneumonia, especially SPP. Importantly, miR-1271-5p showed high diagnostic value of SPP, with the AUC of 0.877, the sensitivity of 74.9% and specificity of 87.8%. The results of multivariate logistic analysis demonstrated that miR-1271-5p was an independent risk factor for progression to SPP. Elevated serum miR-1271-5p levels were associated with poor prognosis in children with pneumonia and possessed predictive value for patients' adverse outcomes. CONCLUSION: Elevated serum miR-1271-5p was demonstrating superior diagnostic and prognostic specificity in severe pediatric pneumonia, providing a potential biomarker.
MiR-100-5p is involved in severe pneumonia in children by targeting MTOR.
Zhang L, Wang Q, Mo S
BMC Immunol · 2026 May · PMID 42210076 · Full text
BACKGROUND: Severe pneumonia in children is a life-threatening respiratory condition that can lead to severe complications and even mortality. We confirmed the possibility of miR-100-5p as a biomarker in severe pneumonia...
BACKGROUND: Severe pneumonia in children is a life-threatening respiratory condition that can lead to severe complications and even mortality. We confirmed the possibility of miR-100-5p as a biomarker in severe pneumonia in children. METHODS: A total of 200 children were included. The expression of miR-100-5p from serum was detected. WI-38 cells were treated with 10 µg/mL LPS for 24 h. miR-100-5p was overexpressed or inhibited by transfection. In addition, proliferation and inflammatory factors were measured. TargetScan was utilized to forecast the downstream of miR-100-5p. The targeting relationship between miR-100-5p and MTOR was confirmed by the dual-luciferase reporter system. miR-100-5p and MTOR were co-overexpressed to detect the function of both in severe pneumonia in children. RESULTS: miR-100-5p expression was decreased and had a high diagnostic value in severe pneumonia in children. The miR-100-5p level was closely related to clinical indicators. In WI-38 cells treated with LPS, overexpression of miR-100-5p increased proliferation and reduced inflammatory factors, while inhibition of miR-100-5p reduced proliferation and increased inflammatory factors. MTOR expression was negatively associated with miR-100-5p expression in severe pneumonia in children. CONCLUSIONS: miR-100-5p may participate in severe pneumonia in children by negatively regulating MTOR, proving that it might be a biomarker of severe pneumonia in children.
A conserved capsid-based multi-epitope vaccine targeting dengue virus serotypes (DENV1-4): an integrated computational and in vivo study.
Khatrawi EM, Ali SL, Ali A … +2 more , Ali SM, Althagafi H
BMC Immunol · 2026 May · PMID 42192530 · Full text
BACKGROUND: Dengue virus (DENV), comprising four antigenically distinct serotypes (DENV1-4), continues to pose a major global health burden. The lack of a universally protective vaccine capable of inducing balanced immun...
BACKGROUND: Dengue virus (DENV), comprising four antigenically distinct serotypes (DENV1-4), continues to pose a major global health burden. The lack of a universally protective vaccine capable of inducing balanced immunity against all serotypes remains a critical challenge, largely due to antigenic diversity and the risk of antibody-dependent enhancement (ADE). Conserved capsid proteins represent promising targets for epitope-based vaccine development because of their structural stability and immunogenic potential. METHODS: An integrated reverse vaccinology and immunoinformatics strategy was employed to design a conserved capsid-based multi-epitope vaccine (MEV-DV) targeting DENV1-4. B-cell, cytotoxic T-lymphocyte (CTL), and helper T-lymphocyte (HTL) epitopes were screened for antigenicity, non-allergenicity, non-toxicity, and sequence conservancy. Selected epitopes were assembled using appropriate linkers with β-defensin as an adjuvant and a PADRE sequence. The construct was evaluated for physicochemical properties, 3D structure modeling and validation, solubility, disulfide engineering, molecular docking with TLR4 and TLR8, molecular dynamics simulation, and immune simulation. Experimental validation was performed in albino mice using an alum-adjuvanted formulation, and humoral responses were assessed by hemagglutination inhibition (HI) assay. RESULTS: The finalized MEV-DV construct exhibited high antigenicity (0.8559), favorable physicochemical properties, and structural stability, with 97.6% of residues located in favored Ramachandran regions. Docking studies demonstrated strong binding affinity with TLR4 and TLR8, and molecular dynamics simulations confirmed stable receptor-vaccine interactions over 50 ns. Immune simulations predicted robust humoral and cellular immune responses with sustained memory formation. In vivo immunization induced detectable antibodies by day 7, with peak HI titers at day 21. Antibody levels were statistically comparable to those elicited by a commercial inactivated dengue vaccine (p > 0.05), and no adverse effects were observed. CONCLUSION: This study demonstrates that a conserved capsid-based multi-epitope vaccine designed through reverse vaccinology and immunoinformatics is structurally stable, immunogenic, and safe in a murine model. The combined computational and experimental findings support the potential of MEV-DV as a promising broadly protective dengue vaccine candidate and warrant further evaluation through neutralization assays and viral challenge studies.
Immunoinformatic design of a multi-epitope vaccine candidate targeting multidrug-resistant Pseudomonas aeruginosa.
Babaei M, Shahbazi B, Sarkoohi P … +3 more , Azadi A, Ranjbar KJ, Ahmadi K
BMC Immunol · 2026 May · PMID 42185761 · Full text
BACKGROUND: Pseudomonas aeruginosa, a World Health Organization (WHO) priority pathogen, causes severe multidrug-resistant (MDR) infections in immunocompromised and hospitalized patients, highlighting the critical need f...
BACKGROUND: Pseudomonas aeruginosa, a World Health Organization (WHO) priority pathogen, causes severe multidrug-resistant (MDR) infections in immunocompromised and hospitalized patients, highlighting the critical need for effective vaccines. To this end, we designed a novel multi-epitope vaccine by integrating immunodominant domains from three key virulence proteins (PcrV, OprE, and CupC2) with the cholera toxin B subunit (CTB) as a mucosal adjuvant. METHODS: Immunoinformatics was used to predict epitopes and construct a vaccine with EAAAKEAAAK linkers. In silico assessments included antigenicity, allergenicity, solubility, molecular docking with TLR2/TLR4, 150 ns MD simulations, PDBsum interaction analysis, and C-ImmSim immune profiling. RESULTS: Both the adjuvanted and non-adjuvanted candidates were predicted to be non-allergenic, with antigenicity scores of 0.6557 and 0.7338, respectively, indicating strong immunogenic potential. Both constructs were also predicted to exhibit high solubility, with scores exceeding the threshold (0.927 and 0.729). Each vaccine candidate showed robust interactions with TLR2 and TLR4; however, the adjuvanted construct demonstrated superior binding affinity to both receptors. Molecular docking of the adjuvanted vaccine candidate followed by 150 ns molecular dynamics (MD) simulations confirmed stable and strong interactions with TLR2 and TLR4, as evidenced by RMSD values of 0.64 nm and 0.73 nm, and binding energies of ΔG = - 15.9 kcal/mol and - 12.7 kcal/mol, respectively further supporting their high immunogenic potential. Moreover, in silico immune simulation data predicted rapid induction of protective antibodies and cytokines and revealed that adjuvant-enhanced responses substantially improved the stability of the TLR2 complex. CONCLUSION: These computational results suggest that our multi-antigen vaccine candidate may have potential against Pseudomonas aeruginosa infections. Further validation through gene synthesis, murine immunogenicity studies (e.g., BALB/c models), and challenge experiments is required.
Dynamic immune profiling enables early distinction between gastrointestinal GVHD and viral diarrhea after hematopoietic stem cell transplantation.
Chen M, Wang XQ, Long J … +3 more , Fu MJ, Wang H, Zhao W
BMC Immunol · 2026 May · PMID 42185760 · Full text
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for hematologic malignancies, yet diarrhea after allo-HSCT-mainly due to gastrointestinal graft-versus-host disease (GI-GVHD) or vira...
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for hematologic malignancies, yet diarrhea after allo-HSCT-mainly due to gastrointestinal graft-versus-host disease (GI-GVHD) or viral infection-remains a major clinical challenge. Early etiological differentiation is essential for appropriate management. AIMS: This study aimed to develop an immune-based predictive model by dynamically monitoring lymphocyte subsets and cytokines after allo-HSCT. RESULTS: Among 232 patients who underwent allo-HSCT at Beijing Lu Daopei Hospital between 2021 and 2024, 58 developed biopsy-confirmed post-transplant (post-HSCT) diarrhea, comprising 34 cases of GI-GVHD and 24 cases of viral enteritis. Immune profiles were measured one week prior to diarrhea onset, as well as at weeks 4 and 5 post-HSCT. Predictive features were selected using LASSO and logistic regression to construct single- and multi-time-point models, which were validated using nomogram, calibration, and decision curve analyses. At the pre-diarrhea point, patients with aGVHD had higher Reg3α, CD3⁺T%, CD8⁺T%, naive CD4⁺/CD4⁺T%, and Th2/CD4⁺T%, but lower NK count and NK% (all P < 0.05). The single-time-point model achieved good discrimination (AUC = 0.799), while the multi-time-point model integrating nine dynamic parameters showed superior accuracy (AUC = 0.908). CONCLUSIONS: Dynamic immune profiling may aid in the early distinction between GI-GVHD and viral enteritis, highlighting its potential as a tool for immunological surveillance to guide intervention after allo-HSCT.
Deficient TRPM3-linked mitochondrial Ca influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome.
Magawa CT, Eaton-Fitch N, Muraki K … +1 more , Marshall-Gradisnik S
BMC Immunol · 2026 May · PMID 42177403 · Full text
INTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic illness, commonly associated with dysregulation of the immune system including reduced cytotoxicity of natural killer (NK) cell...
INTRODUCTION: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic illness, commonly associated with dysregulation of the immune system including reduced cytotoxicity of natural killer (NK) cells and post-exertional neuroimmune exhaustion. Previously, transient receptor potential melastatin 3 (TRPM3) ion channel impairment associated with reduced Ca mobilisation in NK cells from ME/CFS patients was reported. To further explore the pathomechanisms involved in ME/CFS, we investigated the downstream impact of TRPM3 ion channel dysfunction on mitochondrial Ca mobilisation in NK cells. METHOD: Fluorescence live-cell imaging was used to investigate Ca mobilisation in NK cells of (N = 10) ME/CFS, classified using Canadian Consensus Criteria, and (N = 10) healthy control (HC) participants. Cytoplasmic and mitochondrial Ca entry was determined using Fluo-8 AM and Rhod-2 AM Ca indicators, respectively. The effect of TRPM3 modulation on Ca mobilisation ex vivo, was examined using pregnenolone sulfate and ononetin to activate and inhibit the channel, respectively. RESULTS: Cytosolic Ca influx amplitude and slope were significantly reduced (p < 0.001), with a significantly shorter T response (p = 0.001) in ME/CFS compared to HC. Ca influx amplitude (p < 0.001) and slope (p < 0.041) into the mitochondria were significantly higher in ME/CFS compared to HC. TRPM3 activation triggered pronounced cytosolic response (P < 0.001) accompanied by mitochondrial Ca increase in HC. TRPM3-dependent cytosolic and mitochondrial Ca mobilisation (P < 0.015) were significantly reduced with a shorter T response (p < 0.02) in ME/CFS compared to HC. CONCLUSION: The results demonstrate that altered TRPM3-mediated cytosolic Ca influx may significantly impact Ca mobilisation into the mitochondria of people with ME/CFS. Alterations that interfere with the optimal function of Ca permeable channels may cumulatively impact downstream signalling, leading to detrimental cellular consequences. Collectively these findings provide an avenue for further studies on the physiological functions of TRPM3 ion channel and its role in ME/CFS.
Elevated CDYL expression in the peripheral blood of patients with rheumatoid arthritis.
Xu M, Xia X, Yang J … +5 more , Zhao L, Xu J, Wang S, Cui D, Peng H
BMC Immunol · 2026 May · PMID 42174416 · Full text
BACKGROUND: Chromodomain Y-like protein (CDYL), a member of the CDY-related gene family, plays a pivotal role in nervous diseases, reproductive systems and tumors by chromatin remodeling and disrupting normal transcripti...
BACKGROUND: Chromodomain Y-like protein (CDYL), a member of the CDY-related gene family, plays a pivotal role in nervous diseases, reproductive systems and tumors by chromatin remodeling and disrupting normal transcriptional regulation. However, the expression and biological functions of CDYL in rheumatoid arthritis (RA) remain unclear. This study aims to investigated the role of CDYL in the pathogenesis of RA. METHODS: A cohort of 43 RA patients and 36 healthy subjects were included in the study. The transcript levels of CDYL, interleukin-17 A (IL-17 A) and IL-22 were detected by quantitative real-time PCR. Flow cytometry and Western blot were used to analyze the relationship between CDYL and Th17 cells. The GSE100191 dataset from the GEO database was downloaded to conduct a comprehensive bioinformatics analysis of the potential functions of CDYL. The interaction of CDYL and EZH2 and the effects of the EZH2 antagonist on Th17 cells were measured by Western blot. RESULTS: The CDYL was highly expressed in the PBMCs derived from RA patients, exhibiting positive correlations with DAS28 score (r = 0.36, p < 0.0177) and serum anti-cyclic citrullinated peptide antibody titers (r = 0.4255, p = 0.004). Moreover, the transcript levels of CDYL were positively correlated with elevated IL-17 A levels (r = 0.5140, p < 0.001) and IL-22 (r = 0.4540, p = 0.002) levels in RA patients and the RA dataset. CDYL expression is markedly upregulated in Th17 cells, while the proportion of Th17 cells is increased in RA patients. Mechanistically, CDYL knockdown significantly inhibited Th17 differentiation in vitro, which suggests that CDYL is associated with and functionally contributes to the differentiation of Th17 cells. CONCLUSIONS: Our findings indicate that CDYL expression is associated with and promotes the differentiation of Th17 cells in RA patients and may be involved in the process of RA.
Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.
Al Ameer HJ, Jyothi S R, Ahmad IA … +6 more , Patro PS, Arora V, Singla S, Tulkin T, Arslanbekovna AF, Kumar-Mishra M
Immunology · 2026 May · PMID 42171955 · Publisher ↗
Autophagy is a central cellular process that supports homeostasis, yet it also plays a critical part in tumour immune evasion and treatment resistance, creating substantial obstacles for contemporary cancer immunotherapy...
Autophagy is a central cellular process that supports homeostasis, yet it also plays a critical part in tumour immune evasion and treatment resistance, creating substantial obstacles for contemporary cancer immunotherapy. Because of this dual nature, targeted modulation of autophagy in either tumour cells or immune cells holds considerable potential to enhance therapeutic outcomes. However, the successful integration of autophagy directed strategies requires a clearer understanding of the molecular pathways through which autophagy shapes immune activity and treatment response. A more refined view of autophagy within the tumour immune microenvironment may open new therapeutic opportunities. Selectively targeting specific autophagy pathways could help overcome immune resistance and strengthen the impact of immunotherapy. Progress in this field will likely depend on the development of delivery systems that allow precise control of tumour autophagy in a compartment specific manner, as well as combination approaches that complement emerging treatments. Incorporating insights from immuno oncology, metabolic regulation, and immune surveillance may accelerate the translation of novel autophagy modulators into clinical testing, although current progress remains shaped largely by preclinical and early translational evidence.
Gastric Cancer-Derived Exosomal MATN3 Favours Immunosuppressive Tumour Microenvironment by Activating Autophagy in an EGFR/ELK1/ATG12 Signalling Dependent Manner.
Zhao Q, Liu S, She X … +4 more , Ma S, Tang H, Peng D, Guo H
Immunology · 2026 May · PMID 42163458 · Publisher ↗
Gastric cancer (GC)-derived exosomes (Exos) have been identified to facilitate GC progression by inducing M2 macrophage polarization. This study investigated the biological function of exosomal matrilin-3 (MATN3) in M2 m...
Gastric cancer (GC)-derived exosomes (Exos) have been identified to facilitate GC progression by inducing M2 macrophage polarization. This study investigated the biological function of exosomal matrilin-3 (MATN3) in M2 macrophage polarisation during GC development and its underlying mechanism. Exos were isolated from GC cells and then co-cultured with THP-1-derived macrophages. Macrophage polarisation was evaluated by measuring the levels of M1/M2 macrophage markers. Target molecule expression was evaluated by RT-qPCR, Western blotting and immunohistochemical staining. LC3II expression and the co-localisation of MATN3 and epidermal growth factor receptor (EGFR) were determined by immunofluorescent staining. In vivo growth of GC cells was assessed in a xenograft mouse model. Molecular mechanisms were analysed by Co-IP, ChIP, dual-luciferase reporter assay and ubiquitination assay. MATN3 was highly expressed in GC and its high expression was negatively associated with the overall survival and M1 macrophage marker expression of GC patients. The in vitro experiments validated that MATN3 was secreted by GC-Exos, which promoted M2 macrophage polarisation via autophagy activation. In addition, exosomal MATN3 contributed to in vivo growth of GC cells via promoting M2 macrophage infiltration. Mechanistically, MATN3 interacted with EGFR to enhance its protein stability, which activated Ets-like protein-1 (ELK1) and consequently promoted ATG12-mediated autophagy. Activation of the EGFR/ELK1 pathway abolished exosomal MATN3 silencing-mediated inhibitory effect on autophagy and M2 macrophage polarisation. GC-derived exosomal MATN3 exerted an oncogenic role by inducing M2 macrophage polarisation via activation of the EGFR/ELK1/ATG12 axis-mediated autophagy, which provides potential therapeutic targets for GC.
Genetic susceptibility and HLA association in autoimmune hepatitis among Yemeni patients.
Farie WQ, Bahaj SS, Al-Madhagi AK … +3 more , Ali SS, Noman A, Alkassar WY
BMC Immunol · 2026 May · PMID 42163120 · Full text
BACKGROUND: Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver disease characterized by the progressive destruction of hepatocytes, often leading to cirrhosis and liver failure. Genetic predisposition, partic...
BACKGROUND: Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver disease characterized by the progressive destruction of hepatocytes, often leading to cirrhosis and liver failure. Genetic predisposition, particularly the involvement of human leukocyte antigen (HLA) alleles, is well-documented in the pathogenesis of AIH. However, the specific HLA associations in the Yemeni population remain unexplored, despite increasing clinical evidence of AIH in this region. OBJECTIVE: This study aims to elucidate the distribution of HLA class alleles in Yemeni patients (aged ≥ 18 years) with AIH and assess their association with disease susceptibility, contributing to the growing body of immunogenetic research in Middle Eastern populations. METHODS: This case-control study included 93 AIH patients and 280 healthy controls (total N = 373), all of Yemeni origin. We conducted high-resolution HLA typing and compared the frequencies of HLA alleles with global data. Allelic distributions were analyzed for associations with AIH susceptibility, and findings were interpreted in the context of previously identified genetic markers of autoimmune liver disease. RESULTS: The most frequent allele in Yemeni AIH patients was HLA-DRB1*03:01 (42.5% vs. 15.5% in controls, OR = 4.0, 95% CI = 2.8-5.8, p = 0.01), followed by HLA-DRB1*04:01 (21.5% vs. 16.9%, OR = 1.3, 95% CI = 1.1-2.0, p = 0.04) and HLA-A*02 (31.7% vs. 27.9%, OR = 1.2, 95% CI = 1.1-1.3, p = 0.001). Protective alleles such as HLA-DRB1*13:01 were significantly more frequent in controls (13.2% vs. 3.8%, OR = 0.3, 95% CI = 0.1-0.6, p = 0.001). Our results demonstrate a genetic predisposition to AIH in Yemen, primarily associated with the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles. The observed distribution aligns with international trends but also reveals distinct ethnic-specific patterns that warrant further investigation. CONCLUSION: This study highlights the critical role of HLA-DRB1* alleles, particularly DRB1*03:01 and DRB1*04:01, in the genetic susceptibility to AIH in the Yemeni population. These findings not only enhance the understanding of genetic factors in AIH but also establish a foundation for future immunogenetic research in the Middle East. The identification of region-specific HLA associations could inform both diagnostic and therapeutic strategies for AIH in Yemen and similar populations. This study was restricted to adults (≥ 18 years); therefore, findings may not apply to pediatric AIH.
Current Status of Treg Therapy in Transplantation and Autoimmune Disease.
Li H, Zeng H
Immunology · 2026 May · PMID 42159047 · Publisher ↗
Regulatory T cells (Tregs) represent a critical subset of T lymphocytes essential for maintaining immune homeostasis. Through diverse molecular mechanisms, Tregs exert potent immunosuppressive effects that preserve self-...
Regulatory T cells (Tregs) represent a critical subset of T lymphocytes essential for maintaining immune homeostasis. Through diverse molecular mechanisms, Tregs exert potent immunosuppressive effects that preserve self-tolerance and mitigate aberrant immune activation. Dysregulation in Treg frequency or function is closely associated with the development of various immune-mediated disorders. This has prompted extensive preclinical investigations and clinical trials evaluating the therapeutic potential of Tregs in conditions such as graft-versus-host disease, solid organ transplantation, and autoimmune diseases, which have yielded promising outcomes. This review provides a comprehensive overview of current preclinical and clinical applications of Treg-based therapies, including adoptive Treg transfer, low-dose IL-2, and CAR-Treg therapy, and discusses their effectiveness in modulating immune responses across diverse pathological contexts.
Protein homeostasis as a determinant of CD8⁺ T cell fate.
Chang YT, Richter FC, Jiang W
Nat Rev Immunol · 2026 Jul · PMID 42156576 · Publisher ↗
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The immunology of human breast cancer.
García-Torralba E, Loi S, Salgado R … +2 more , Galluzzi L, Buqué A
Nat Rev Immunol · 2026 May · PMID 42151556 · Publisher ↗
Over recent years, immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various solid neoplasms, including melanoma and lung carcinoma. A proportion of these malignancies e...
Over recent years, immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various solid neoplasms, including melanoma and lung carcinoma. A proportion of these malignancies exhibit a baseline immunological configuration that can be successfully targeted with ICIs to support durable clinical responses. Conversely, breast neoplasms other than the triple-negative subset respond poorly to ICIs, reflecting numerous tumour-intrinsic and microenvironmental barriers against effective anticancer immunity. Notably, most hormone receptor-positive breast cancers tend to have limited immunogenicity and to establish a local and systemic immunosuppressive microenvironment that hinders responses to ICIs. Here, we summarize the main immunological features of human breast tumours, whenever possible comparing across disease subtypes, stages and treatment outcomes. Understanding the complex interplay between breast cancer, its hormonal regulation and the immune system will be essential for unlocking the full potential of ICIs and other immunotherapies in this oncological indication.
IL-21 rs2055979 and serum IL-21 levels are associated with both non-segmental and segmental vitiligo in an Iranian cohort.
Gholijani N, Dehghan Z, Abolmaali SS … +3 more , Talepoor AG, Yazdani M, Daryabor G
BMC Immunol · 2026 May · PMID 42144579 · Full text
BACKGROUND: Vitiligo is an autoimmune disorder primarily categorized into non-segmental (NSV) and segmental (SV) subtypes. Interleukin-21 (IL-21) is a pleiotropic cytokine implicated in immune dysregulation. OBJECTIVE: T...
BACKGROUND: Vitiligo is an autoimmune disorder primarily categorized into non-segmental (NSV) and segmental (SV) subtypes. Interleukin-21 (IL-21) is a pleiotropic cytokine implicated in immune dysregulation. OBJECTIVE: To investigate the association of serum IL-21 levels and two genetic variants (rs2055979 and rs4833837) with susceptibility to NSV and SV in an Iranian cohort. METHODS: The study included 264 vitiligo patients (225 NSV, 39 SV) and up to 390 healthy controls. Serum IL-21 was measured by ELISA. Genotyping for rs2055979 was performed by RFLP-PCR, and for rs4833837 by ASO-PCR. RESULTS: Serum IL-21 levels were significantly elevated in both NSV (median 71.50 pg/mL) and SV (median 65.35 pg/mL) patients compared to controls (median 18.70 pg/mL; p < 0.0001). For rs2055979, the GT genotype was associated with increased risk of NSV (unadjusted OR = 2.99, 95% CI = 1.86-4.80, p < 0.0001; age- and sex-adjusted OR = 1.809, 95% CI = 1.061-3.085, p = 0.029) and SV (unadjusted OR = 4.29, 95% CI = 1.45-12.7, p = 0.005; adjusted OR = 3.486, 95% CI = 1.006-12.077, p = 0.049). The unadjusted G allele was a risk factor for NSV (OR = 1.52, 95% CI = 1.19-1.94, p = 0.0009) but not for SV (p = 0.09). The GG genotype also conferred elevated unadjusted risk for NSV (OR = 2.51, 95% CI = 1.44-4.37, p = 0.0009). In contrast, rs4833837 showed no significant association with either vitiligo subtype. CONCLUSION: The IL-21 rs2055979 polymorphism is associated with vitiligo susceptibility, with the GT genotype representing a risk factor for both NSV and SV after adjustment for age and sex. The marked elevation of serum IL-21 in both NSV and SV further supports a pathogenic role for IL-21, suggesting the IL-21/IL-21R axis as a potential therapeutic target.
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