Myosin 1f and Proline-rich 13 are transcriptionally upregulated yet functionally redundant in CD4+ T cells during blood-stage Plasmodium infectionAsatsuma, Moreira, Lee
et alPLoS One (2025) 20 (3), e0320375
Abstract: Plasmodium-specific CD4+ T cells differentiate into effector and memory subsets during experimental malaria, via mechanisms that remain incompletely characterised. By mining scRNA-seq data of CD4+ T cells during Plasmodium chabaudi chabaudi AS infection in mice, we identified two genes previously uncharacterised in T helper cells, long-tailed unconventional myosin 1f (Myo1f) and proline-rich13/taxanes-resistance 1 (Prr13/Txr1), which were upregulated during effector and memory differentiation. Myo1f is reported to regulate motility and granule exocytosis in myeloid and γδ T cells. Prr13/Txr1 is reported to transcriptionally regulate sensitivity to anti-cancer drugs. To test for cell-intrinsic gene function, we generated Plasmodium-specific TCR transgenic, PbTII cells harbouring CD4-promoter driven Cre recombinase and target genes with loxP-flanked essential exons. We validated our approach for the transcription factor Maf, formally demonstrating here that cMaf is essential for T follicular helper (Tfh) cell differentiation in experimental malaria. Next, having generated conditional knockout lines for Myo1f and Prr13, we observed that deficiency in Myo1f or Prr13 had no impact on either clonal expansion, Th1/Tfh differentiation or transit to memory. Additionally, despite continued expression during re-infection, Myo1f was unnecessary for Th1 recall in vivo. Thus, while cMaf is critical for Tfh differentiation in experimental malaria, Myo1f and Prr13, although transcriptionally upregulated, are unnecessary for effector or memory CD4+ T cell responses.Copyright: © 2025 Asatsuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Bacterial vaginosis associates with dysfunctional T cells and altered soluble immune factors in the cervicovaginal tractMacLean, Tsegaye, Graham
et alJ Clin Invest (2025)
Abstract: Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually-acquired HIV, yet the immunological mechanisms underlying this association are not well understood.To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, Kinga Study participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples.High-parameter flow cytometry revealed an increased frequency of cervical conventional CD4+ T cells (Tconv) expressing CCR5. However, we found no difference in number of CD3+CD4+CCR5+ cells in the CX or VT of BV+ versus BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV have an increased frequency of dysfunctional CX and VT CD39+ Tconv and CX tissue-resident CD69+CD103+ Tconv, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations.Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.
When estrogen deficiency meets immune responses induced by rabies vaccinationQian, Zhang, Tian
et alMicrobiol Spectr (2025)
Abstract: Estrogen deficiency in postmenopausal women is accompanied by immune status alterations, leading to a chronic low-grade inflammatory phenotype. Immediate rabies postexposure prophylaxis (PEP) following a transdermal bite or scratch from a rabies-infected animal is urgently needed. However, whether immune alterations in postmenopausal women influence the reaction to rabies vaccination remains unclear. Bilateral ovariectomized (OVX) and Sham mice were immunized with modified live vaccine RABV LBNSE. LBNSE immunization had no obvious pathological effect on the mice in either group and effectively protected all mice from RABV attack. Although 100% protection was found, the reduction rate of viral neutralizing antibody titers in the LBNSE-OVX mice was greater than that in the LBNSE-Sham mice. LBNSE immunization recruited/activated fewer dendritic cells (DCs) and B cells in the lymph nodes, while more B cells were detected in the blood of LBNSE-OVX mice than in that of LBNSE-Sham mice. Th1 and Th2 immune responses are both rapidly induced in LBNSE-OVX-subjected mice and are inclined toward a Th2-biased immune response. LBNSE immunization in OVX mice elicited similar amounts of RABV-specific CD4+ and CD8+ T cells as those in Sham mice. Our data revealed that the protective efficacy of rabies vaccination was slightly decreased by estrogen deficiency and that DC and B lymphocyte recruitment/activation and Th-mediated responses in splenocytes were partly altered; however, rabies vaccination offered sufficient protection against RABV within the observation period, helping alleviate anxiety related to rabies virus exposure after menopause. Additional measures might be helpful to improve long-term effective protection in postmenopausal women.IMPORTANCEMenopause has a distinct effect on the decrease in the female immune system, and whether protection efficacy after rabies vaccination in postmenopausal women is influenced requires evaluation. Our findings demonstrated that although viral neutralizing antibody (VNA) titers in the LBNSE-OVX mice were similar to those in the LBNSE-Sham mice, VNAs declined faster than those in the LBNSE-Sham mice within the observation period. Fewer dendritic cells in the lymph nodes were recruited/activated in LBNSE-OVX mice than in LBNSE-Sham mice, whereas B cells in the lymph nodes and peripheral blood exhibited the opposite tendency. Th2-biased immune responses were induced in LBNSE-OVX mice, and no significant changes were observed in RABV-specific CD4+ or CD8+ T cells. These results provide evidence that rabies vaccination could provide effective protection for postmenopausal women within the observation period, but other measures might be needed to improve protection, which is beneficial for alleviating anxiety of menopausal women when facing rabies immunization.
Prognosis model of patients with breast cancer based on metabolism-related LncRNAsZhang, Ma, Yang
et alDiscov Oncol (2025) 16 (1), 390
Abstract: Metabolism-related lncRNAs may play a significant role in the occurrence and development of breast cancer. This study aims to identify metabolism-related lncRNAs with high predictive value for prognosis and to construct a model that can predict the prognosis of breast cancer individually.Transcriptome data and clinical data of patients with breast cancer were retrieved from the TCGA database, and metabolism-related genes were sourced from the GSEA database. Metabolism-related lncRNAs in breast cancer were obtained through differential expression analysis and Pearson correlation analysis. Prognostic-related lncRNAs were further screened using Univariate Cox regression and LASSO regression. Kaplan-Meier survival analysis was performed and the survival curve of the two groups was drawn. Univariate and Multivariate Cox regression analyses were conducted to identify the independent prognostic factors, which were subsequently integrated into a nomogram for individualized prognostic prediction.Through differential analysis, 2135 differential lncRNAs were obtained, of which 231 were metabolism-related lncRNAs. Using Univariate Cox regression and LASSO regression, a risk prediction model incorporating 19 metabolism-related lncRNAs was constructed. The survival curve suggested that patients with high-risk scores had a poor prognosis compared to those with low-risk scores (P < 0.05). Cox regression analysis further identified that age, stage classification, distant metastasis and risk score as independent prognostic factors to construct a nomogram. KEGG pathway enrichment analysis revealed that differential lncRNAs may be related to JAK-STAT signaling pathway, MAPK signaling pathway and mTOR signaling pathway. Finally, based on the analysis of the CIBERSORT algorithm, lncRNAs used in the construction of the model had a strong correlation with CD8+T cells, activated CD4+T cells and the polarization of M2 macrophages.Bioinformatics methods were utilized to identify metabolism-related lncRNAs associated with breast cancer prognosis, and a prognostic risk model was constructed, laying a solid foundation for the study of metabolism-related lncRNAs in breast cancer.© 2025. The Author(s).
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