Severe COVID-19 associates with humoral immune response dysregulation. While antibodies confer protection against SARS-CoV-2, evidence also support their putative contribution to disease severity. Our study demonstrates that higher levels of S2-IgG, and S2-, RBD-, and Nucleocapsid-IgA differentiate severe and non-severe cases. However, no major antibody functional differences are found between both COVID-19 manifestations. Enhanced Fc-dependent functions in severe cases are primarily driven by increased antibody titers. No differences in antibody avidity are found between severe and non-severe cases, but a gradation in binding strength across specificities suggests that early anti-RBD, -S2, and -Nucleocapsid antibodies may originate from different pathways. In golden Syrian hamsters, S2 immunization or transfer of RBD-depleted antibodies isolated from severe and non-severe cases promote a faster clinical recovery after SARS-CoV-2 challenge, despite a transient initial weight loss. These findings indicate that antibodies are not major determinants of COVID-19 severity and suggest additional factors influencing disease outcomes.
© 2025. The Author(s).

Sertoli cells (SCs) are somatic cells that are a part of the seminiferous tubules in the testes and support germ cell development and maturation. Additionally, SCs play another role in protecting male germ cells from immune destruction via the formation of the blood-testis barrier and the secretion of several immunoregulatory factors. Based on these characteristics, SCs have been suggested to create a tolerogenic environment to protect co-transplanted cells as immune modulators. Because mature SCs are quiescent somatic cells and show lower proliferation activity in vitro, it is difficult to obtain the number of human cells needed for clinical applications.
We established a protocol for mass production of SCs from human ESCs (hESC-SCs) and their functional properties were analyzed in vitro and in diabetic-induced mice after their co-transplantation with human insulin-secreting cells.
hESC-SCs were successfully produced via a stepwise differentiation protocol. In addition, a mass culture method was established to secure the number of hESC-SCs available for cell therapy. hESC-SCs obtained from in vitro derivation highly express marker genes of SCs, such as GATA4, SOX9, CLDN11, and AR, and have shown immune-modulation activity similar to that of human bone marrow-mesenchymal stem cells. In diabetic-induced mice subcutaneously co-transplanted with EndoC-βH1 cells (insulin-secreting cells) and hESC-SCs, lower blood glucose levels were maintained for 6 months than in those transplanted with EndoC-βH1 cells alone.
We believe that hESC-SCs could be useful tool for securing cell therapy to treat human diseases in the future.
© 2025. The Author(s).

Engineered stone silicosis is an interstitial lung disease that progresses rapidly; in many cases, it can cause respiratory insufficiency and death. The metabolic activities occurring in the lungs and adenopathies, as well as their relationships with systemic inflammation, are unknown. Patients with complicated silicosis were enrolled in this study. All of the patients had worked for at least 5 years in finishing and installing engineered stone and had not been exposed to these working conditions for at least 7 years. Clinical data measurements, positron emission tomography/computed tomography using 18F-fluorodeoxyglucose (18F-FDG PET/CT), respiratory function tests and blood samples were performed. The mean age of the patients was 44 ± 5.4 years. Moreover, the average exposure duration was 10.94 ± 3.2 years, and the average number of years from cessation of exposure was 11.6 ± 1.6 years. The average maximum standardized uptake value (SUVmax) of large opacities was 6.32 ± 3. All of the patients demonstrated hypermetabolic mediastinal lymphadenopathies, and 88.2% of the patients also demonstrated extrathoracic lymphadenopathies. The SUVmax of the large opacities was correlated with fibrinogen (ρ = 0.717, P = 0.001), the lymphocyte-to-monocyte ratio (ρ = - 0.506, P = 0.038), the systemic inflammatory response index (ρ = 0.559, P = 0.02) and CD4+NKT cells. Large areas of lung opacity and lymphadenopathies exhibited high metabolic activities years after the cessation of silica exposure. The relationships between metabolic activity and several inflammatory factors may lead to the exploration of new therapeutic targets.
© 2025. The Author(s).

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive primary intestinal lymphoma with a poor prognosis. MEITL can metastasize to the central nervous system, liver and spleen, but gallbladder involvement has not yet been reported. The present study describes the case of a 57-year-old woman who presented with abdominal distention, pain and vomiting. Contrast-enhanced computed tomography revealed thickening and perforation of the small intestinal wall, and a gallbladder mass. Histopathological analysis of the affected small intestine and gallbladder revealed a dense infiltrate of medium-sized monomorphic lymphocytes with a CD3+, CD4-, CD8+ and TIA-1+ phenotype. Based on the absence of celiac disease, aggressive clinical course, and characteristic histopathological and immunophenotypic features, a diagnosis of MEITL with gallbladder involvement was established. The patient underwent small intestinal resection and cholecystectomy, followed by chemotherapy, which was completed without gastrointestinal or gallbladder perforation. Diagnostic resection is currently the best approach for suspected malignant lymphoma of the gallbladder. This rare case of MEITL with gallbladder involvement highlights the importance of considering this diagnosis in similar clinical scenarios and the role of cholecystectomy, which can serve both diagnostic and therapeutic purposes.
Copyright: © 2025 Okuda et al.

The close association between nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) infection highlights the potential of therapeutic vaccination against viral antigens as an attractive immunotherapy for treating EBV+ NPC. Maximizing vaccine efficacy often requires selecting optimal T cell epitopes and incorporating co-treatment strategies. Here, we analyzed genomic mutations of 283 cancer-associated EBV strains and predicted epitopes with broad human leukocyte antigen (HLA) coverage from high-frequency nonsynonymous mutations. A polyepitope mRNA vaccine constructed from the predicted epitopes elicited antigen-specific T cell responses but showed suboptimal efficacy in tumor control in a PBMC-humanized mouse EBV+ NPC model. To enhance treatment efficacy, we developed an optimized system for expanding human natural killer (NK) cells with high purity and cytotoxicity as a co-treatment modality. Combined administration of mRNA vaccine and NK cells synergistically improved therapeutic efficacy by durably suppressing or eradicating NPC tumors in humanized mice. The concurrent treatment could improve the infiltration of both human T cells and NK cells into the tumor microenvironment and boost their effector functions. Our study suggests the combined therapeutic vaccination and NK cell therapy as a potential strategy for treating EBV+ NPC.
© 2025 The Author(s).