CD4+ follicular regulatory T (Tfr) cells control B cell responses through the modulation of follicular helper T (Tfh) cells and germinal center development while suppressing autoreactivity; however, their role in the regulation of productive germinal center B cell responses and humoral memory is incompletely defined. We show that Tfr cells promote antigen-specific germinal center B cell responses upon influenza virus infection. Following viral challenge, we found that Tfr cells are necessary for robust generation of virus-specific, long-lived plasma cells, antibody production against both hemagglutinin (HA) and neuraminidase (NA), the two major influenza virus glycoproteins, and appropriate regulation of the BCR repertoire. To further investigate the functional relevance of Tfr cells during viral challenge, we used a sequential immunization model with repeated exposure of antigenically partially conserved strains of influenza viruses, revealing that Tfr cells promote recall antibody responses against the conserved HA stalk region. Thus, Tfr cells promote antigen-specific B cell responses and are essential for the development of long-term humoral memory. 相似文献
The number of adolescent refugees around the world has been continuously increasing over the past few years trying to escape war and terror, among other things. Such experience not only increases the risk for mental health problems including anxiety, depression, and post-traumatic stress disorder (PTSD), but also may have implications for socio-cognitive development. This study tested cognitive-affective processing in refugee adolescents who had escaped armed conflict in Syria and now resided in Istanbul, Turkey. Adolescents were split into a high trauma (n = 31, 12 girls, mean age = 11.70 years, SD = 1.15 years) and low trauma (n = 27, 14 girls, mean age = 11.07 years, SD = 1.39 years) symptom group using median split, and performed a working memory task with emotional distraction to assess cognitive control and a surprise faces task to assess emotional interpretation bias. The results indicated that high (vs. low) trauma symptom youth were ~ 20% worse correctly remembering the spatial location of a cue, although both groups performed at very low levels. However, this finding was not modulated by emotion. In addition, although all youths also had a ~ 20% bias toward interpreting ambiguous (surprise) faces as more negative, the high (vs. low) symptom youth were faster when allocating such a face to the positive (vs. negative) emotion category. The findings suggest the impact of war-related trauma on cognitive-affective processes essential to healthy development.
To validate a simultaneous analysis tool for the brain and cervical cord embedded in the statistical parametric mapping (SPM) framework, we compared trauma‐induced macro‐ and microstructural changes in spinal cord injury (SCI) patients to controls. The findings were compared with results obtained from existing processing tools that assess the brain and spinal cord separately. A probabilistic brain‐spinal cord template (BSC) was generated using a generative semi‐supervised modelling approach. The template was incorporated into the pre‐processing pipeline of voxel‐based morphometry and voxel‐based quantification analyses in SPM. This approach was validated on T1‐weighted scans and multiparameter maps, by assessing trauma‐induced changes in SCI patients relative to controls and comparing the findings with the outcome from existing analytical tools. Consistency of the MRI measures was assessed using intraclass correlation coefficients (ICC). The SPM approach using the BSC template revealed trauma‐induced changes across the sensorimotor system in the cord and brain in SCI patients. These changes were confirmed with established approaches covering brain or cord, separately. The ICC in the brain was high within regions of interest, such as the sensorimotor cortices, corticospinal tracts and thalamus. The simultaneous voxel‐wise analysis of brain and cervical spinal cord was performed in a unique SPM‐based framework incorporating pre‐processing and statistical analysis in the same environment. Validation based on a SCI cohort demonstrated that the new processing approach based on the brain and cord is comparable to available processing tools, while offering the advantage of performing the analysis simultaneously across the neuraxis. 相似文献
Erenumab is a monoclonal antibody blocking the calcitonin gene–related peptide receptor, which has been approved for the preventive treatment of chronic migraine (CM). The aim of this study was to explore the safety and effectiveness of erenumab in patients suffering from CM and medication overuse headache (MOH) in a real-life setting, up to 1 year.
Methods
Data regarding 81 patients treated with erenumab were retrospectively analyzed. Every 3 months, the following variables were collected: the mean number of headache days per month (headache index (HI)), the average number of painkillers taken per month (analgesic consumption (AC)), the mean number of days with painkiller consumption (number of days on medication (NDM)), the headache intensity (numeric rating scale (NRS) score), the 6-item Headache Impact Test (HIT-6), and the Self-Reported Instrument to Assess Work-Related Difficulties in Patients With Migraine (HEADWORK) scores.
Results
The HI, AC, and NDM and the NRS, HIT-6, and HEADWORK scores were significantly lower at every time point from the 3rd month onward compared to baseline (all P < 0.0001). No significant differences were found between patients who underwent painkiller detoxification before starting erenumab and those who did not (all P > 0.05). No significant differences were found between patients taking erenumab in combination with other preventive treatments and the ones taking it alone (all P ≥ 0.05). Five patients dropped out because of adverse events, which resolved after stopping erenumab.
Conclusion
Erenumab was safe and effective for CM complicated with MOH. Painkiller withdrawal and the association with other preventive treatment(s) seem useless.
Tumor progression is deeply influenced by epigenetic changes induced by tumor stroma. Cancer-associated fibroblasts (CAFs) have been reported to promote epithelial–mesenchymal transition in cancer cells, thereby enhancing their aggressiveness and stem-like properties. As CAFs are able to recruit endothelial progenitor cells (EPCs) to tumor site, we aim to investigate their interplay for prostate carcinoma progression. Both prostate CAFs and cancer cells actively recruit EPCs, known to affect tumor progression through increased vasculogenesis. EPCs synergize with CAFs to further promote epigenetic plasticity of cancer cells, through a mesenchymal-to-amoeboid transition. Indeed, after fibroblasts have engaged epithelial–mesenchymal transition in cancer cells, a further shift towards amoeboid motility is promoted by EPCs through contact-mediated triggering of the bidirectional ephrinA1/EphA2 signaling. The activation of ephrinA1 reverse pathway enhances EPC-induced neo-vascularization, thus promoting tumor growth, while EphA2 forward signaling elicits mesenchymal–amoeboid transition in cancer cells, favoring their adhesion to endothelium, transendothelial migration, and lung metastatic colonization. We therefore underscore that the metastatic advantage given by tumor microenvironment embraces different motility strategies and propose EphA2-targeted tools as useful adjuvants in anti-metastatic treatments. 相似文献