Immunology & Cell Biology最新文献

The discourse surrounding gender equity has intensified recently, amplified by the impacts of the COVID-19 pandemic, highlighting the critical underrepresentation of women in leadership roles across various sectors including the media and healthcare. In medical research, this disparity is particularly pronounced, with women often excluded from senior positions despite their substantial presence in the workforce. This review seeks to explore the multifaceted issue of gender inequity in medical research leadership, examining the systemic barriers that women face, the socioeconomic factors that compound these challenges and the global variations in leadership representation of women. Diverse leadership teams are essential for fostering medical innovation, improving patient outcomes and ensuring that clinical trials and medical research are effective, inclusive and representative. The underrepresentation of women in leadership roles is not merely a matter of gender bias; it is intricately linked to socioeconomic factors that hinder their advancement. Women from lower socioeconomic backgrounds face additional obstacles, such as limited access to education and professional networks, which further exacerbate their underrepresentation in leadership positions. Moreover, cultural and societal norms play a significant role in shaping the career trajectories of women. As a group of immunologists, including representatives of the International Union of Immunological Sciences (IUIS) Gender Equity Committee, we review the causes of these inequities. We examine the impact of gender-diverse leadership on pre-clinical and medical research, emphasizing the need for inclusive leadership to drive progress in medical research and resulting healthcare. Finally, the review proposes strategies for improving gender equity in medical research leadership, including policy changes, organizational initiatives and societal shifts. By addressing these critical issues, this review contributes to the ongoing efforts to promote gender equity in medical research, ultimately enhancing the quality and inclusiveness of scientific inquiry and its impact on healthcare delivery.

In this article, we discuss a recent study, where autosomal monoallelic expression of genes underlying Inborn Errors of Immunity were investigated. About 2-10% of genes are predominantly transcribed from a single allele leading to autosomal random monoallelic expression (I). If this is skewed in a cell population from an individual with an autosomal dominant inborn error of immunity, this can lead to a mild to no phenotype (incomplete penetrance) if the wildtype allele is favored (II), or to more severe disease presentation if the variant allele is favored (III).

In this article, we discuss a recent article by Jia et al., where high OLAH expression was detected in severe and fatal respiratory disease which was associated with a number of processes and responses. These include high abundance of oleic acid, excessive cytokine release, high viral titres and lipid droplets and increased presence of lung-associated innate cells.

Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity. We integrated functional assays for NK cells cultured in a variety of cytokine combinations with mathematical modeling using feature selection and mechanistic regression models. Our regression model successfully predicts NK cell proliferation for different cytokine combinations and indicates synergy of activated STATs and NF-κB transcription factors between priming and post-priming phases. The use of IL-21 in solution in the priming of NK cell culture resulted in an improved NK cell proliferation, without compromising cytotoxicity potential or interferon gamma secretion against hepatocellular carcinoma cell lines. Our work provides an integrative framework for interrogating NK cell proliferation and activation for cancer immunotherapy.

AT7519, which inhibits multiple cyclin-dependent kinases, has been extensively investigated in various types of cancer cells. Previous studies have demonstrated the ability of this molecule to suppress the expression of the nuclear receptor retinoic acid–related orphan receptor gamma (RORγ) and several genes involved in hepatocellular carcinoma progression. In this study, we identified a distinct agonistic effect of AT7519 on RORγt, an isoform expressed by various immune cells, including T helper 17 lymphocytes. These immune cells play pivotal roles in shaping the tumor microenvironment and promoting the anticancer response of the immune system. After exposure to AT7519 during differentiation, primary human CD4⁺ T cells presented increased expression of IL17A/F, IFNG and GZMB and decreased expression of PDCD1 and CTLA4. These findings elucidate a previously unrecognized facet of AT7519 activity and suggest the potential incorporation of this molecule into immune therapies to augment the effectiveness of diverse anticancer strategies involving anti–programmed cell death protein 1 (anti–PD-1) and anti–cytotoxic T-lymphocyte antigen 4 (anti–CTLA4) regimens.

Immunology & Cell Biology 2025; 103: 213; https://doi.org/10.1111/imcb.12855

Correction to: Immunology & Cell Biology 2024; https://doi.10.1111/imcb.12826

The name of one of the authors is incorrect. Ning Ming should be Ning Meng. The correct spelling of this author's name appears in the title above.

In this Research Highlight, we discuss recent research which shows that TCR-mediated activation and NF-κB signalling play an indispensable role in localising Xist RNA and its interactors to the inactive X chromosome (Xi) in T cells (left and middle). Inhibition of NF-κB disrupts this process, impairing the recruitment of silencing factors and jeopardizing the maintenance of X chromosome inactivation (right).

This report presents findings from a group of UK-based researchers with expertise in the use of animal models for bone marrow ablation and reconstitution. The primary aim is to facilitate the implementation of the Three Rs (Replacement, Reduction and Refinement), with an emphasis on refinement. Bone marrow ablation and reconstitution procedures are performed for a number of different purposes and conducted predominantly in mice. These procedures can induce significant suffering, classified as "severe", Category E or Category D/E under European, US and Canadian legislation, respectively. Although severity categorization is not mandated in countries such as Australia and New Zealand, legislation still requires that the level of animal suffering must be minimized to the greatest extent possible. This report identifies specific animal welfare issues and proposes practical measures aimed at reducing both animal use and suffering.

Pursuing an international scientific career is a fantastic opportunity for personal and professional growth, but it also poses unique challenges, which can be particularly daunting for researchers coming from resource-limited countries. Drawing from personal experience, this article provides insights into navigating the transition to working abroad in academia and developing a sustainable career while integrating into a new culture. From predeparture preparations to achieving career independence, I discuss practical aspects of crafting tailored applications to contact potential advisers, contemplating visa-related challenges, establishing collaborations and emphasizing the value of finding appropriate mentorship to help you adapt to new cultural and professional environments. The article also underscores the importance of resilience, adaptability and redefining career success as a dynamic, nonlinear process. I present an original perspective on career planning, inspired by maritime voyage planning, to address the complexities of balancing personal and professional life, particularly during transitional periods. This approach, which combines four key stages of planning, namely, appraisal, planning, execution and monitoring, serves as a model for early-career researchers to navigate the unpredictable tides of academic work and personal life abroad with the goal of sustaining progress and well-being. These reflections aim to empower scientists preparing for or adapting to international research environments, fostering resilience and adaptability for long-term success abroad.