Immunology & Cell Biology最新文献

Positive research cultures provide the environment for scientists to explore ideas, grow as individuals, develop team science and create a positive impact on those around them. While positive research cultures need to grow from the kindness and integrity of team members, organization policy can either help or hinder this organic positive behavior. A focus on policies to enhance positive research culture can benefit even high-functioning organizations, by expanding and extending the benefits. Here we focus on key actionable areas to create and reinforce a positive research culture in your organization. We discuss the role of aligning staff recognition to the organization's missions, the influence of the organization unit and career structure on the research culture, the pyramid of building respectful interactions, the value of openness and transparency and the overarching goal of equality, diversity and inclusivity within the organization.

Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared with people with higher SES. Age, sex, host genetics, smoking and cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo-rating system using socioeconomic features such as education, income and home ownership status to objectively rank SES in the 1000 donors. We observed sex-specific SES associations, such as females with a low SES having a significantly higher frequency of CMV seropositivity compared with females with high SES, and males with a low SES having a significantly higher frequency of active smoking compared with males with a high SES. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES-dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind SES effects on immune responses and ultimately disease.

The ability to characterize immune cells and explore the molecular interactions that govern their functions has never been greater, fueled in recent years by the revolutionary advance of single-cell analysis platforms. However, precisely how immune cells respond to different stimuli and where differentiation processes and effector functions operate remain incompletely understood. Inferring cellular fate within single-cell transcriptomic analyses is now omnipresent, despite the assumptions typically required in such analyses. Recently developed experimental models support dynamic analyses of the immune response, providing insights into the temporal changes that occur within cells and the tissues in which such transitions occur. Here we will review these approaches and discuss how these can be combined with single-cell technologies to develop a deeper understanding of the immune responses that should support the development of better therapeutic options for patients.

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.

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.