Immunological Reviews最新文献

Elimination of tumors is typically dependent on T cells, which require prior or ongoing activation signals. These dependencies form the basis for our understanding of “tumor-reactive immunity” and for the successes of immunotherapies, particularly immune checkpoint blockades. Over the years, tremendous work has been done towards understanding the biology of this reactive immunity and early investigation identified dendritic cells (DC) as key contributors. Recent advances have shed more light on dendritic cell heterogeneity in tumors, revealing specialized roles for each subtype. In addition, the network of cellular interactions surrounding DCs has grown as additional cell types have been revealed to variously influence how the immune system can become most effective at eliminating malignancies. Greater understanding of intratumoral DC biology has empowered investigators to engineer dendritic cell vaccines and consider other approaches to augment this component of reactive immunity, towards the generation of anti-tumor immune responses de novo. In this review, we will discuss the state of the field, recent advances and suggest what the near future of scientific inquiry could entail.

Dendritic cells (DCs) are central regulators of the delicate balance between protective immune responses to pathogens and cancer, and immunopathology. This review explores the phenotypic and functional heterogeneity of DCs and their specialized roles in regulating the immune response, with a focus on pathways that confer tolerogenic properties to DCs. Furthermore, we discuss emerging strategies for the therapeutic induction of a tolerogenic phenotype in DCs in the setting of autoimmune diseases. A better understanding of the molecular mechanisms that control the tolerogenic phenotype of DCs may open new avenues for the development of efficacious and safe immunotherapies for autoimmune, allergic, and chronic inflammatory diseases.

Dendritic cells (DCs) are central to vertebrate immunity, bridging innate and adaptive responses. While DC biology has been extensively studied in mammals, how this cell population is evolutionarily developed and adapted to the ancient immune system of the non-mammalian vertebrates remains poorly understood. Fish, the earliest vertebrates with a fully developed adaptive immune system, offer unique opportunities to explore the evolutionary emergence and diversification of DCs. Early studies in fish, relying on conserved phenotypical markers and morphological observations, hinted at the existence of DC-like populations but lacked definitive validation. Recent advances in single-cell transcriptomics, combined with powerful genetic resources in model organisms like zebrafish, enable the precise identification and characterization of these cells. In this review, we summarize the historical and current understanding of DCs in fish, with a particular focus on zebrafish studies. We highlight both conserved and species-specific features of their development and function, and further elaborate on two special DC populations that are unique to fish. By integrating evolutionary immunology with cutting-edge technologies, zebrafish DC research is poised to provide fundamental insights into antigen-presenting cell biology.

Dendritic cells (DCs) demonstrate remarkable functional and metabolic heterogeneity that governs the balance between immune tolerance and autoimmune pathogenesis. Under homeostatic conditions, tolerogenic DC subsets maintain immunological equilibrium through distinct metabolic programs and the production of immunoregulatory metabolites, promoting T cell anergy and regulatory T cell (Treg) differentiation. In contrast, autoimmune conditions trigger pathogenic metabolic rewiring, shifting DCs toward glycolysis and enhanced lipid synthesis, which drives DC hyperactivation and breakdown of self-tolerance. This metabolic reprogramming is coordinately regulated by external microenvironmental cues and internal signaling pathways, leading to heterogeneous DC responses in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and psoriasis. Targeting metabolic regulators offers promising therapeutic strategies to restore immune tolerance and prevent harmful autoimmunity and inflammation. The review highlights the intricate interplay between DC metabolism and function, emphasizing how metabolic heterogeneity underpins their dual roles in immune regulation and autoimmunity. Future exploration of subset-specific metabolic preferences and spatiotemporal metabolic dynamics will facilitate the development of precision immunotherapies for autoimmune diseases.

Upon activation, B cells integrate signals from antigen and T cell help to choose between a rapid extrafollicular (EF) response and entry into the germinal center (GC). EF differentiation produces short-lived plasmablasts that provide immediate but relatively low-affinity antibody, whereas GC entry commits B cells to iterative selection, somatic hypermutation, and affinity maturation, ultimately yielding high-affinity plasma cells and memory B cells. At the B–T cell border, where both responses originate, B cells also undergo class switch recombination (CSR). In this review, we examine the molecular mechanisms of CSR, highlighting the interplay between the DNA deaminase AID, transcription, and noncanonical nucleic acid structures. We further discuss the differential requirement of glycolysis between the EF versus GC response and how the cytokine IL-21 fine-tunes B cell entry into the GC. Together, these perspectives integrate genomic alterations, metabolic demands, and cytokine-mediated signaling at the critical decision point between EF and GC pathways.