Trends in Immunology最新文献

Adjuvants are critical to improving the magnitude, breadth, functionality, and durability of vaccine immunogenicity. Despite advances in vaccinology, long-term immunity, variant cross-protection, and robust mucosal responses remain unmet goals. These challenges underscore the need for novel, safe, and effective adjuvants. This review explores emerging adjuvants targeting specific immune pathways. We highlight clinical and preclinical studies focusing on adjuvants that enhance durable and persistent humoral, cellular, and mucosal immunity. Current trends are discussed alongside tailored approaches for children and the elderly. Finally, the aim of this review is to highlight novel vaccine adjuvants currently in preclinical and clinical development, with the potential to generate a vaccine platform fit for the necessary yet unmet needs of public health in a postpandemic era.

Type 2 immunity protects against helminths and venoms, yet its dysregulation drives allergic diseases. Initiation occurs at barrier tissues, where epithelial cells detect perturbations and release alarmins, activating type 2 innate lymphoid cells and conditioning dendritic cells for T helper 2 priming. However, the framework of type 2 innate immune sensing remains largely incomplete. Critical gaps include the core immunostimulatory components of many stimuli and their host detection pathways. Recent advances, including tuft cell chemosensation, membrane pore formation as a common trigger, and the role of protein crystals and proteases in allergic inflammation, highlight emerging molecular principles. Unlike bacterial, viral, and fungal recognition via conserved molecular patterns, type 2 immunity often involves the sensing of perturbations and stress signals.

Deciphering how mRNA vaccines generate humoral immunity could accelerate next-generation vaccine design. Castaño et al. reveal that mRNA-lipid nanoparticle vaccines employ a dual-adjuvant mechanism: nucleoside-modified mRNA triggers type I interferons to mature dendritic cells, while lipid nanoparticles induce a pro-T follicular helper cell program, together promoting robust germinal center responses.

While artificial intelligence (AI) is transforming biological science, its full potential in immunology has yet to be realized due to limited data and the need for extensive experimental validation. This review provides a practical guide for experimental immunologists to actively contribute to AI development, with a focus on applications for B- and T-cell receptors. It not only gives an overview of common AI techniques in immunology but also highlights the important role of high-throughput experimental methodologies. Overall, we believe that the synergy between AI and experimental innovation will be a crucial catalyst for advancing the field of immunology.

Cheng et al.'s recent study identifies the Cullin3-RING E3 ubiquitin ligase complexes (CRL3) adaptor protein Kelch-like protein 6 (KLHL6) as a proteostasis regulator whose downregulation in chronically stimulated T cells leads to the accumulation of thymocyte selection-associated high mobility group box protein and phosphoglycerate mutase family member 5, driving T-cell dysfunction. This work positions T-cell exhaustion as a proteostatic disorder and highlights KLHL6 as a promising target for cancer immunotherapy.

IgE contributes to allergy, but its cellular sources are rare and hard to identify. Genetic fate mapping and single-cell sequencing approaches have now revealed that two cell populations maintain IgE: long-lived IgE plasma cells (PCs) and 'type 2' memory B cells. This forum piece discusses recent discoveries on long-lived IgE PCs.

The immunological synapse (IS) formed between cytotoxic CD8⁺ T lymphocytes (CTLs) and tumor cells represents the critical interface where many immunotherapies act, including therapeutic antibodies and chimeric antigen receptor immunotherapy. However, detailed characterization of the CTL-tumor IS has remained limited, primarily due to the transient and dynamic nature of this structure. Recent advances in proteomics, transcriptomics, high-throughput imaging, and machine learning are now enabling more precise investigation of this complex cell-cell interaction. This review highlights how emerging technologies have advanced our understanding of the CTL-tumor IS, outlines their potential to inform next-generation immunotherapies, and proposes future directions for technological innovation.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that primarily affects the skin, joints, and entheses. Growing evidence implicates alterations at the gut and skin barriers in PsA pathogenesis. These sites play a crucial role in tissue homeostasis, and their disruption can contribute to the translocation of immune cells and bacterial products, resulting in systemic inflammation. Crosstalk between barrier sites and joints can promote or exacerbate disease development, with barriers also being a potential target of disease. This review article provides a barrier-centered perspective across gut, skin, and synovium, with a specific focus on new concepts about intertissue communication involving immune and microbial mediators that can propagate inflammation in PsA.

The rapid development of allogeneic engineered therapeutic cells has intensified the challenge of host immune-mediated rejection. Advances in molecular immunology, genetic engineering, and induced pluripotent stem cell-based multigene editing have enabled the creation of 'stealth' allogeneic cells designed to evade immune detection while maintaining function. Key strategies include the deletion of human leukocyte antigen class I and class II molecules to limit T cell recognition, the expression of natural killer (NK) cell inhibitory ligands to prevent NK cell-mediated killing, and the upregulation of CD47 to suppress phagocytosis. An expanding repertoire of immune-modulatory molecules, receptor-ligand interactions, and experimental assays is refining these approaches. Together, stealth designs are accelerating the translation of allogeneic cell therapies toward more durable and broadly applicable clinical use.