Immunology & Cell Biology最新文献

CD8⁺ T cells recognizing their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide–major histocompatibility complex (pMHC) complex. Advances in single-cell sequencing have increased accessibility toward identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8⁺ T-cell population with specificity for a hepatitis C virus (HCV)–derived human leukocyte antigen (HLA) class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent before infection and underwent expansion and stable maintenance for at least 2 years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterized by an unusually long dissociation time (half-life = 794 s and k_off = 5.73 × 10⁻⁴) for its target antigen when compared with previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggested that high-affinity TCR–pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalized immunotherapies.

In this article for the Highlights of 2023 Series, significant advancements in pediatric immunology are discussed, focusing on new diagnostic and therapeutic approaches. Key studies include the integration of genomic and proteomic profiling for better diagnosis of inborn errors of immunity, the impact of nongenetic factors such as autoantibodies on immune responses, the promising use of Janus kinase inhibitors and chimeric antigen receptor-T cell therapy for treating immune deficiencies and autoimmune diseases and the potential for a curative approach using prime editing. These developments mark a shift toward personalized and precision medicine in pediatric immunology.

In this article, I aim to give some pieces of career advise for young immunologists based on my own experiences.

Asking the right questions during a job interview helps you find the best person for your team. A well-crafted question will allow the applicants to shed light on their skills and their passion for science. Just as importantly, good interview questions can let you know about the applicants’ support expectations and needs, and their approach to lab citizenship and research culture. Here we crowd-sourced the #ImmunologyFutures community for their go-to job interview questions, to help you find the right candidate for your position.

M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B-cell lymphoma-3 (Bcl-3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl-3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl-3 in macrophages can regulate glycolysis-related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl-3 was able to promote the interferon gamma/lipopolysaccharide-induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl-3 may be a candidate gene for regulating M1 polarization in macrophages.

Background: Although the unique sexual and reproductive health needs of adolescents and youth (AY) are widely recognized, the challenge remains how to integrate adolescent- and youth-friendly health services (AYFHS) effectively within a systems-based approach that is both feasible and scalable. This article provides preliminary evidence from 4 Nigerian states that sought to overcome this challenge by implementing capacity-strengthening approaches centered around a shortened quality assurance (QA) tool that has become part of the state health system's routine supportive supervision process and follow-up quality improvement (QI) activities.

Methods: A shortened QA tool was administered to assess and track the performance of 130 high-volume health facilities across 5 domains to serve its AY population with quality contraceptive services. Facility-based providers (N=198) received training on adolescent and youth sexual and reproductive health, AYFHS, and long-acting reversible contraceptive methods. To corroborate checklist findings, we conducted exit interviews with 754 clients (aged 15-24 years) who accessed contraceptive services from the facilities that met the World Health Organization's minimum standards for quality AYFHS.

Results: In the 4 states, the QA tool was applied at baseline and 2 rounds, accompanied by QI capacity strengthening after each round. At baseline, only 12% of the 130 facilities in the 4 states scored met the minimum quality standards for AYFHS. After 2 rounds, 88% of the facilities met the minimum standards. AY client volume increased over this same period. All 4 states showed great improvements; however, the achievements varied by state. The exit interview feedback supported client satisfaction with the services provided to AY.

Conclusion: Integrating QA followed by QI within Nigeria's family planning supportive supervision system is not only feasible but also impacts the quality of AYFHS and contraceptive uptake by clients aged 15-24 years.

Delta inulin, or Advax, is a polysaccharide vaccine adjuvant that significantly enhances vaccine-mediated immune responses against multiple pathogens and was recently licensed for use in the coronavirus disease 2019 (COVID-19) vaccine SpikoGen. Although Advax has proven effective as an immune adjuvant, its specific binding targets have not been characterized. In this report, we identify a cellular receptor for Advax recognition. In vitro uptake of Advax particles by macrophage cell lines was substantially greater than that of latex beads of comparable size, suggesting an active uptake mechanism by phagocytic cells. Using a lectin array, Advax particles were recognized by lectins specific for various carbohydrate structures including mannosyl, N-acetylgalactosamine and galactose moieties. Expression in nonphagocytic cells of dendritic cell–specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), a C-type lectin receptor, resulted in enhanced uptake of fluorescent Advax particles compared with mock-transfected cells. Advax uptake was reduced with the addition of ethylenediaminetetraacetic acid and mannan to cells, which are known inhibitors of DC-SIGN function. Finally, a specific blockade of DC-SIGN using a neutralizing antibody abrogated Advax uptake in DC-SIGN–expressing cells. Together, these results identify DC-SIGN as a putative receptor for Advax. Given the known immunomodulatory role of DC-SIGN, the findings described here have implications for the use of Advax adjuvants in humans and inform future mechanistic studies.

Women are more prone to develop rheumatoid arthritis, with peak incidence occurring around menopause. Estrogen has major effects on the immune system and is protective against arthritis. We have previously shown that treatment with estrogen inhibits inflammation and joint destruction in murine models of arthritis, although the mechanisms involved remain unclear. Fibroblastic reticular cells (FRCs) are specialized stromal cells that generate the three-dimensional structure of lymph nodes (LNs). FRCs are vital for coordinating immune responses from within LNs and are characterized by the expression of the chemokine CCL19, which attracts immune cells. The aim of this study was to determine whether the influence of estrogen on innate and adaptive immune cells in arthritis is mediated by estrogen signaling in FRCs. Conditional knockout mice lacking estrogen receptor α (ERα) in CCL19-expressing cells (Ccl19-CreERα^fl/fl) were generated and tested. Ccl19-CreERα^fl/fl mice and littermate controls were ovariectomized, treated with vehicle or estradiol and subjected to the 28-day-long antigen-induced arthritis model to enable analyses of differentiated T- and B-cell populations and innate cells in LNs by flow cytometry. The results reveal that while the response to estradiol treatment in numbers of FRCs per LN is significantly reduced in mice lacking ERα in FRCs, estrogen does not inhibit joint inflammation or markedly affect immune responses in this arthritis model. Thus, this study validates the Ccl19-CreERα^fl/fl strain for studying estrogen signaling in FRCs within inflammatory diseases, although the chosen arthritis model is deemed unsuitable for addressing this question.

We studied the associations between inflammation-related proteins in circulation and complications after pediatric allogenic hematopoietic stem cell transplantation (HSCT), to reveal proteomic signatures or individual soluble proteins associated with specific complications after HSCT. We used a proteomics method called Proximity Extension Assay to repeatedly measure 180 different proteins together with clinical variables, cellular immune reconstitution and blood viral copy numbers in 27 children (1–18 years of age) during a 2-year follow-up after allogenic HSCT. Protein profile analysis was performed using unsupervised hierarchical clustering and a regression-based method, while the Bonferroni-corrected Mann–Whitney U-test was used for time point–specific comparison of individual proteins against outcome. At 6 months after allogenic HSCT, we could identify a protein profile pattern associated with occurrence of the complications such as chronic graft-versus-host disease, viral infections, relapse and death. When protein markers were analyzed separately, the plasma concentration of the inhibitory and cytotoxic T-cell surface protein FCRL6 (Fc receptor-like 6) was higher in patients with cytomegalovirus (CMV) viremia [log₂-fold change 1.5 (P = 0.00099), 2.5 (P = 0.00035) and 2.2 (P = 0.045) at time points 6, 12 and 24 months]. Flow cytometry confirmed that FCRL6 expression was higher in innate-like γδ T cells, indicating that these cells are involved in controlling CMV reactivation in HSCT recipients. In conclusion, the potentially druggable FCRL6 receptor on cytotoxic T cells appears to have a role in controlling CMV viremia after HSCT. Furthermore, our results suggest that system-level analysis is a useful addition to the studying of single biomarkers in allogenic HSCT.

The May–June 2024 issue of Immunology & Cell Biology contains an Immunology Futures Special Feature on Disability Inclusion in Science. Diverse groups do better in science, yet individuals with disabilities face barriers to accessing education and opportunities within scientific disciplines. The Monash Sensory Science program, led by Professor Jamie Rossjohn and legally blind artist in residence Dr Erica Tandori, has transformed the accessibility for those with blindness, low vision and diverse needs (BLVDN) to experience biomedical data visualization through the form of multisensory scientific communication. The Monash Sensory Science Exhibition, first hosted in 2018 with the support of Monash University and the Australian Research Council, utilizes tactile multisensory and multimodal artworks, interactive displays and multisensory science books for BLVDN participants. In this Special Feature, scientists and researchers involved in the 2023 Autoimmunity Monash Sensory Science Exhibition discuss the novel models and displays designed to improve the scientific understanding of complex autoimmune diseases including rheumatoid arthritis, lupus, celiac disease, psoriasis and type 1 diabetes. This Special Feature aims to inform the inclusive teaching of immunology and raise discussions of how to improve access to all within our scientific institutions.