Infectious tolerance: mechanisms of self-propagating immune regulation

There have been increasing reports that durable tolerance to foreign proteins, tissue transplants, and autoimmune targets can be induced or restored through therapeutic intervention. Although these responses may persist for extended periods, they can depend on the continued presence of antigen and on the establishment of regulatory networks within the host. In many models, tolerance induction involves regulatory T cells, including Tr1 cells and FoxP3+ CD4+ T cells, whereas other approaches rely on the deletion, exhaustion, or functional inactivation of antigen-specific effector cells. Importantly, accumulating evidence suggests that the initial tolerising intervention may trigger secondary host-derived mechanisms that actively propagate and maintain tolerance. This self-sustaining, “contagious” process, commonly termed infectious tolerance, remains incompletely understood. Defining how regulatory cells, tissues, and local microenvironments cooperate to establish long-term tolerance is therefore an important priority for immunology and translational medicine.This Research Topic aims to define the cellular, molecular, and tissue-level mechanisms that enable tolerance to spread beyond the initial tolerising event and persist within the host. We particularly welcome studies addressing how antigen-specific regulatory cells influence neighbouring or newly recruited immune cells, how linked suppression is established, and how tolerogenic networks are maintained in the absence of the original therapeutic intervention. Contributions may examine preclinical and clinical models involving transplantation, autoimmune disease, allergy, or immune responses to therapeutic proteins. Studies should investigate the secondary events that contribute to the infectiousness of tolerance, including the emergence of regulatory or pro-tolerogenic cell populations, changes in antigen presentation, and the development of tissue microenvironments that support immune regulation. Understanding these processes may identify strategies to amplify infectious tolerance and improve the durability, safety, and clinical applicability of tolerance-inducing therapies. To gather further insights into host-mediated mechanisms that initiate, propagate, and sustain infectious tolerance, this Research Topic will focus on mechanistic studies across experimental and clinical settings rather than on disease-specific therapeutic outcomes alone. We welcome Original Research, Reviews, Perspectives, Brief Research Reports, and Methods articles addressing, but not limited to, the following themes:• Induction, expansion, and stability of host-derived regulatory T cells, including Tr1 and FoxP3+ T cells• Linked suppression and the transfer of tolerance between antigen-specific and bystander immune cells• Emergence and function of other pro-tolerogenic populations, including regulatory B cells, tolerogenic dendritic cells, macrophages, and myeloid-derived suppressor cells• Antigen presentation, epitope spreading, and mechanisms that extend tolerance beyond the initial target antigen• Contributions of stromal, endothelial, epithelial, and parenchymal tissue cells to tolerance maintenance• Metabolic, transcriptional, and epigenetic reprogramming associated with tolerogenic microenvironments• Tissue homeostasis, immune privilege, and local niches that support long-term immune regulation• Microbiota, soluble mediators, extracellular vesicles, and cellular communication in infectious tolerance• Preclinical and clinical evidence for infectious tolerance in transplantation, autoimmune disease, allergy, and responses to therapeutic proteins• Therapeutic strategies to induce, reinforce, or amplify self-propagating tolerance safely and durably Topic editors: Herman Waldmann, Lucienne Chatenoud Source: https://www.frontiersin.org/research-topics/85707/infectious-tolerance-mechanisms-of-self-propagating-immune-regulation