This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8⁺ T cells was tested by blocking IL-10 in vitro. The percentage of CD19⁺CD5⁺CD1d⁺ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8⁺ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8⁺ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8⁺ T cells.

In our study, we investigated whether circulating T follicular helper (Tfh) and the related cytokines are involved in human cystic echinococcosis (CE). A total of 64 patients with CE and 30 healthy controls were enrolled in this study. Percentages of CCR7loPD-1hi cells within CXCR5+ CD4+ T cells (circulating Tfh cells) were detected by flow cytometry. Levels of IL-21 and IL-4 in peripheral blood were detected by cytometric bead array. The mRNA expression of IL-21, IL-4, Bcl-6, and Blimp-1 in peripheral blood mononuclear cells (PBMCs) were measured by real-time PCR. Levels of IgG1, IgG2, IgG3, and IgG4 in the patients’ sera were measured using enzyme-linked immunosorbent assay. Percentages of circulating Tfh cells were significantly increased in the CE1, CE2, and CE3 groups (p < 0.05). The concentrations of IL-21 and IL-4 in the serum were significantly increased in CE1, CE2, and CE3 groups (p < 0.05). IL-21 was positively correlated with circulating Tfh cells in CE3 group (r = 0.779, p < 0.05). The mRNA levels of IL-21, IL-4, and Bcl-6 were increased in CE1, CE2, and CE3 groups. Levels of IgG1 and IgG4 in patients’ sera were increased in CE1, CE2, and CE3 groups. Levels of IgG2 and IgG3 were increased in CE4-5 group. Additionally, after stimulation with hydatid fluid in vitro, the levels of circulating Tfh cells, IL-21 and IL-4 in PBMCs isolated from CE patients were significantly increased (p < 0.05). The levels of circulating Tfh and related cytokines were significantly increased in CE patients, suggesting that they are involved in human CE.

Brucella spp., the causative agent of zoonotic brucellosis, poses a significant threat to both animal husbandry and human health. Given the limitations of current antibiotic treatments for human brucellosis, there is an urgent need to develop effective human vaccines. Using reverse vaccinology and bioinformatics approaches, we designed a multi-epitope vaccine (MEV) specifically targeting the CcmA, ccmC, and BepC membrane proteins, with the aim of providing robust protection against human infection.We screened 11 CTL, 9 HTL, 2 conformational B cell epitopes, and 9 linear B cell epitopes, linked them with GGGS,GPGPG and KK. and incorporated HMGN1 (high mobility group nucleosome binding protein 1) as an adjuvant and PADRE (a universal HTL epitope to enhance cross-population immunogenicity) to boost immunogenicity. Analyses showed the 638-amino-acid MEV had high antigenicity (1.2542, exceeded the threshold of 0.4), was non-toxic(ToxinPred2) and non-allergenic(AllergenFP), had low human homology(BLASTP e-value < 0.005), Instability index 26.80 (< 40),and good solubility(0.896, > 0.5).Molecular docking and dynamics confirmed its stability. Codon optimization for E. coli enhanced expression potential. Immunoinformatics simulations showed the MEV effectively increased antibody level,T cell counts, and proinflammatory cytokines.In conclusion, the MEV shows promise for brucellosis vaccine development. To fully assess its efficacy and safety, a series of in vivo experiments will be conducted using animal models, which will serve as a critical step towards validating its potential as a viable vaccine candidate.

The intestinal mucosal immune system maintains homeostasis through complex interactions between epithelial cells and innate lymphoid cells in the lamina propria. Tuft cells, previously overlooked intestinal epithelial cell types, detect parasites and metabolites via Sucnr1 and TAS2R receptors. They secrete IL-25, which activates type 2 innate lymphoid cell (ILC2) via the IL-25R receptor. ILC2 releases IL-13, resulting in further promotion of tuft and goblet cells from stem cells. This positive feedback loop amplifies the local type 2 immune response, combating parasitic infections. Tuft cells also recognize viruses and bacteria, but the role played by the tuft cell-ILC2 circuit in this process is not yet clear. Furthermore, tuft cell-ILC2 circuit is influenced by dietary fiber, intestinal microbiota, and other factors, contributing to new functions in maintaining intestinal homeostasis. In inflammatory bowel disease, this immunological circuit may be protective. This review summarizes the current understanding of the tuft cell-ILC2 circuit, its regulatory mechanisms, and potential implications in intestinal disease. Graphical abstract (by Figdraw 2.0)