Immunology is entering a new technological era. From humanized mouse models and organ-on-chip systems to multi-omic sequencing and spatial transcriptomics, researchers now have unprecedented ways to observe and manipulate the immune system, cell by cell and molecule by molecule. A new Nature Index 2025 Immunology report spotlights how these innovations are redefining experimental design, data analysis, and translational discovery across the field.
THX mice: Bridging the gap between humans and models
Despite decades of refinement, conventional mouse models have always fallen short of replicating the intricacies of human immunity. Mice possess over 1,600 immune-response genes that differ from their human equivalents, limiting their predictive power in vaccine and immunotherapy studies.
Now, a new humanized model known as THX mice is closing that gap. THX mice are engineered with human stem cells that give rise to key immune components, including lymph nodes, antibodies, and T and B cells. When vaccinated with mRNA COVID-19 vaccines, these mice mounted strong antibody responses, offering a realistic platform for studying human immune reactions.
The model is already gaining traction internationally. THX mice promise to be cost-effective, scalable, and highly translational, potentially becoming a new standard for preclinical immune research.
Organ-on-chip and organoid systems: Beyond animal models
A revolution in experimental immunology is underway as scientists move toward miniaturized human systems that mimic real organs and tissues. Using organoid and organ-on-chip technologies, researchers can now simulate the immune interactions of the gut, liver, lung, and reproductive tract, without relying on animal testing.
Researchers have built sophisticated gut models to study microbiome–immune interactions and inflammatory signalling, as well as models of endometriosis and pancreatic cancer. Such human-relevant systems are reshaping both basic immunology and drug discovery.
This shift is accelerating: the U.S. National Institutes of Health (NIH) recently announced that it will no longer fund projects solely reliant on animal models for human disease, prioritizing human-based systems instead. The U.S. Food and Drug Administration (FDA) has followed suit, endorsing organoids and human cell cultures for safety testing. These policies reflect growing recognition that animal studies often fail to predict drug efficacy and toxicity in humans.
Single-cell sequencing and beyond: Seeing the immune system in high definition
Single-cell RNA sequencing (scRNA-seq) has transformed immunology by revealing gene expression in individual cells — uncovering cellular diversity that bulk sequencing once masked. Over the past decade, it has become indispensable for mapping immune landscapes in health and disease.
Now, researchers are pairing scRNA-seq with complementary tools for deeper insights:
- CITE-seq simultaneously identifies cell-surface proteins and RNA, helping researchers classify three main natural killer (NK) cell types and design new multi-targeted NK cell therapies for resistant cancers.
- ATAC-seq reveals which DNA regions are accessible for gene activation, allowing scientists to trace the molecular roots of acute myeloid leukemia relapse after treatment.
- Perturb-seq, which integrates CRISPR gene editing with scRNA-seq, enables large-scale genetic perturbation screening. Researchers have used it to identify key host genes exploited by SARS-CoV-2, paving the way for future antiviral therapies.
While the data from these methods are transformative, they are also immense, often costing upwards of $70,000 per experiment and requiring advanced bioinformatics expertise. Initiatives like PerturbSeq.db, a new global database consolidating single-cell datasets, aim to democratize access and foster reproducibility in this data-rich field.
Spatial transcriptomics: Mapping the immune landscape in tissues
Traditional single-cell sequencing captures gene activity but loses spatial context, the “where” of cellular behaviour. Spatial transcriptomics now bridges that gap by mapping gene expression directly within intact tissues.
Researchers have used this technology to analyse breast cancer biopsies, revealing that tumour regions differ dramatically in their drug sensitivity, even when genetically identical. This granular understanding could revolutionize precision oncology by helping clinicians match therapies to distinct tumour microenvironments.
Researchers are also combining spatial data with AI-driven models to predict how cancers evolve over time, turning static tissue snapshots into dynamic simulations of disease progression.
A new era for immune science
From humanized THX mice and organoid systems to multi-omic sequencing and tissue-level mapping, immunology in 2025 is becoming more integrated, human-relevant, and data-driven than ever before. Together, these innovations are redefining how scientists study infection, immunity, and inflammation, moving the field closer to personalized, predictive, and ethically sustainable research.
As these technologies converge, they not only improve how we model human biology but also promise to accelerate the development of next-generation vaccines, immunotherapies, and regenerative treatments that reshape both medicine and the future of immune science.
Journal article: Nature Index 2025: Immunology — Advanced technologies transforming the field. Nature.
Summary by Stefan Botha
