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Background Immune checkpoint inhibitors can cause various adverse effects. Recently it has been shown that Vogt–Koyanagi–Harada (VKH) disease-like uveitis can occur in patients treated with nivolumab. Case presentation A 69-year-old man developed bilateral panuveitis after nivolumab treatment for recurrent hypopharyngeal cancer. Slit lamp examination revealed bilateral granulomatous keratic precipitates, anterior chamber cells and partial synechiae. Fundus examination revealed bilateral optic disc edema and diffuse serous retinal detachment. His human leukocyte antigen (HLA) typing showed HLA-DRB1*04:05 allele. A lumbar puncture did not demonstrate pleocytosis. Bilateral sub-tenon injections of triamcinolone acetonide were initiated. As his panuveitis did not regress completely, steroid pulse therapy was administered. That therapy led to the resolution of his serous retinal detachment and to rapid improvement in his vision. Following this, we treated him with 50 mg/day of prednisolone for 1 week and then reduced it by 5 mg every week. No bilateral uveitis relapse had occurred by his 3-month follow-up; however, he subsequently died because of his cancer. Conclusion To our knowledge, this is the first report of a patient with NVKH who underwent a lumbar puncture. Unlike VKH, our case did not show meningismus or pleocytosis. NVKH may, therefore, have a different etiology from VKH. In cases of NVKH with posterior uveitis, steroid pulse therapy may be considered as a treatment option, as it is in VKH.

When animals are infected with helminthic parasites, resistant hosts show type II helper T immune responses to expel worms. Recently, natural helper (NH) cells or nuocytes, newly identified type II innate lymphoid cells, are shown to express ST2 (IL-33 receptor) and produce IL-5 and IL-13 when stimulated with IL-33. Here we show the relevant roles of endogenous IL-33 for Strongyloides venezuelensis infection-induced lung eosinophilic inflammation by using Il33–/– mice. Alveolar epithelial type II cells (ATII) express IL-33 in their nucleus. Infection with S. venezuelensis or intranasal administration of chitin increases in the number of ATII cells and the level of IL-33. S. venezuelensis infection induces pulmonary accumulation of NH cells, which, after being stimulated with IL-33, proliferate and produce IL-5 and IL-13. Furthermore, S. venezuelensis infected Rag2–/– mice increase the number of ATII cells, NH cells, and eosinophils and the expression of IL-33 in their lungs. Finally, IL-33–stimulated NH cells induce lung eosinophilic inflammation and might aid to expel infected worms in the lungs.

The Zc3h12a gene in innate immunity Here the zinc finger protein encoded by the Zc3h12a gene is shown to be a ribonuclease with an essential role in modulating innate immune responses. Zc3h12a is inducible by Toll-like receptors, and this new work suggests that it inhibits autoimmune disease by controlling the degradation of mRNAs encoding proinflammatory cytokines. The zinc finger protein Zc3h12a is identified as a ribonuclease that inhibits autoimmune disorders by controlling the degradation of messenger RNAs encoding proinflammatory cytokines. Toll-like receptors (TLRs) recognize microbial components, and evoke inflammation and immune responses 1 , 2 , 3 . TLR stimulation activates complex gene expression networks that regulate the magnitude and duration of the immune reaction. Here we identify the TLR-inducible gene Zc3h12a as an immune response modifier that has an essential role in preventing immune disorders. Zc3h12a -deficient mice suffered from severe anaemia, and most died within 12 weeks. Zc3h12a -/- mice also showed augmented serum immunoglobulin levels and autoantibody production, together with a greatly increased number of plasma cells, as well as infiltration of plasma cells to the lung. Most Zc3h12a -/- splenic T cells showed effector/memory characteristics and produced interferon-γ in response to T-cell receptor stimulation. Macrophages from Zc3h12a -/- mice showed highly increased production of interleukin (IL)-6 and IL-12p40 (also known as IL12b), but not TNF, in response to TLR ligands. Although the activation of TLR signalling pathways was normal, Il6 messenger RNA decay was severely impaired in Zc3h12a -/- macrophages. Overexpression of Zc3h12a accelerated Il6 mRNA degradation via its 3′-untranslated region (UTR), and destabilized RNAs with 3′-UTRs for genes including Il6 , Il12p40 and the calcitonin receptor gene Calcr . Zc3h12a contains a putative amino-terminal nuclease domain, and the expressed protein had RNase activity, consistent with a role in the decay of Il6 mRNA. Together, these results indicate that Zc3h12a is an essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes.

The strongest genetic risk factor of Behçet’s disease (BD) is HLA-B*51 . Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51 . Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75–2.56). Furthermore, within the HLA-B*51 -negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43–3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58–2.06), whereas within the HLA-B*51 -negative population, the modified OR became 4.02 (95% CI: 2.29–7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75–2.56), but not in the Middle East or in Europe.

The induction of T cell-mediated immunity is crucial in vaccine development. The most effective vaccine is likely to employ both cellular and humoral immune responses. The efficacy of a vaccine depends on T cells activated by antigen-presenting cells. T cells also play a critical role in the duration and cross-reactivity of vaccines. Moreover, pre-existing T-cell immunity is associated with a decreased severity of infectious diseases. Many technical and delivery platforms have been designed to induce T cell-mediated vaccine immunity. The immunogenicity of vaccines is enhanced by controlling the kinetics and targeted delivery. Viral vectors are attractive tools that enable the intracellular expression of foreign antigens and induce robust immunity. However, it is necessary to select an appropriate viral vector considering the existing anti-vector immunity that impairs vaccine efficacy. mRNA vaccines have the advantage of rapid and low-cost manufacturing and have been approved for clinical use as COVID-19 vaccines for the first time. mRNA modification and nanomaterial encapsulation can help address mRNA instability and translation efficacy. This review summarizes the T cell responses of vaccines against various infectious diseases based on vaccine technologies and delivery platforms and discusses the future directions of these cutting-edge platforms.

Members of the IRAK family of kinases mediate Toll-like receptor (TLR) signaling. Here we show that IRAK2 was essential for sustaining TLR-induced expression of genes encoding cytokines and activation of the transcription factor NF-κB, despite the fact that IRAK2 was dispensable for activation of the initial signaling cascades. IRAK2 was activated 'downstream' of IRAK4, like IRAK1, and TLR-induced cytokine production was abrogated in the absence of both IRAK1 and IRAK2. Whereas the kinase activity of IRAK1 decreased within 1 h of TLR2 stimulation, coincident with IRAK1 degradation, the kinase activity of IRAK2 was sustained and peaked at 8 h after stimulation. Thus, IRAK2 is critical in late-phase TLR responses, and IRAK1 and IRAK2 are essential for the initial responses to TLR stimulation.

Daniel Kastner, Elaine Remmers and colleagues perform an association study of Behçet's disease based on dense genotyping of immune-related loci. They identify new association signals near genes involved in host response to microbial exposure and extend evidence for shared susceptibility loci with Crohn's disease and leprosy. We analyzed 1,900 Turkish Behçet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51 . In the Turkish discovery set, we identified three new risk loci, IL1A – IL1B , IRF8 , and CEBPB – PTPN1 , with genome-wide significance ( P < 5 × 10 −8 ) by direct genotyping and ADO – EGR2 by imputation. We replicated the ADO – EGR2 , IRF8 , and CEBPB – PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO – EGR2 and IRF8 , and meta-analysis additionally identified RIPK2 and LACC1 . The disease-associated allele of rs4402765, the lead marker at IL1A – IL1B , was associated with both decreased IL-1α and increased IL-1β production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association ( P = 5.89 × 10 −15 ). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behçet's disease susceptibility.

Nobuhisa Mizuki and colleagues report a genome-wide association study for Behçet's disease, a chronic systemic inflammatory disorder, in a Japanese population. They identify variants at IL23R-IL12RB2 and IL10 associated with Behçet's disease. Behçet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions 1 . We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behçet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 ( IL23R - IL12RB2 , rs12119179, P = 2.7 × 10 −8 ) and 1q32.1 ( IL10 , rs1554286, P = 8.0 × 10 −8 ). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R - IL12RB2 , P = 1.9 × 10 −11 , odds ratio = 1.35; rs1800871 in IL10 , P = 1.0 × 10 −14 , odds ratio = 1.45).

DNA vaccines induce adaptive immune responses mainly via induction of type-I interferon. This paper shows that this occurs by a mechanism that is independent of the activation of nucleic acid binding Toll-like receptors. B and CD4 + T cell responses require activation of the TBK pathway in hematopoietic cells, whereas TBK1 in non-hematopoietic cells is critical for the activation of CD8 + T cells. Successful vaccines contain not only protective antigen(s) but also an adjuvant component that triggers innate immune activation and is necessary for their optimal immunogenicity 1 , 2 . In the case of DNA vaccines 3 , this consists of plasmid DNA; however, the adjuvant element(s) as well as its intra- and inter-cellular innate immune signalling pathway(s) leading to the encoded antigen-specific T- and B-cell responses remain unclear. Here we demonstrate in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IκB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA-activated, TBK1-dependent signalling and the resultant type-I interferon receptor-mediated signalling was required for induction of antigen-specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensor—Toll-like receptor 9 (TLR9) or Z-DNA binding protein 1 (ZBP1, also known as DAI, which was recently reported as a potential B-form DNA sensor 4 ). Moreover, bone-marrow-transfer experiments revealed that TBK1-mediated signalling in haematopoietic cells was critical for the induction of antigen-specific B and CD4 + T cells, whereas in non-haematopoietic cells TBK1 was required for CD8 + T-cell induction. These data suggest that TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells.

Background Retinal detachment (RD) requires prompt detection to prevent vision loss. Ultra-widefield (UWF) imaging captures the peripheral retina, and deep learning (DL) may enable automated RD detection. We aimed to systematically review and meta-analyze the diagnostic accuracy of DL applied to UWF images for detecting RD. Methods We systematically searched PubMed, Web of Science, and reference lists (last search 22 May 2025) for diagnostic-accuracy studies evaluating DL models for retinal detachment on UWF images with extractable 2 × 2 data. Two reviewers independently selected studies, extracted data, and assessed risk of bias and concerns regarding applicability using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Sensitivity, specificity, and area under the curve (AUC) were pooled using random-effects models, with subgroup analyses by dataset origin (internal vs. external) and retinal detachment spectrum. Results We included 11 studies (2017–2024) using UWF imaging and DL, with test set sizes ranging from 89 to 6,222 images. The pooled sensitivity and specificity were 0.95 (95% CI, 0.94–0.96) and 0.99 (95% CI, 0.99–0.99); the AUC of the summary receiver operating characteristic (SROC) = 0.9962. Heterogeneity was high (I² = 92% for sensitivity; 90% for specificity). In subgroup analyses, external evaluations showed higher sensitivity than internal ones (0.97 vs. 0.92), with similarly high specificity (both ≈ 0.99). Heterogeneity remained substantial within subgroups. QUADAS-2 indicated a low risk of bias in most domains, with unclear index test risk common due to non-prespecified thresholds. Conclusions DL applied to UWF imaging shows high diagnostic accuracy for RD, with pooled sensitivity and specificity of 0.95 and 0.99, respectively, and an AUC of 0.9962. However, the evidence is limited by substantial heterogeneity, inconsistent index-test reporting, and variation in case spectrum and sample size, which may constrain generalizability. Overall, these findings suggest that DL combined with UWF imaging is likely to serve as a valuable adjunctive tool for RD detection and triage, particularly in settings where rapid, wide-field assessment is needed. Registration UMIN-CTR UMIN000057903; PROSPERO CRD420251058209.