From dirty microbiota to immune tolerance: regulatory T cells and anti-inflammatory networks in re-wilded and humanized animal models

Modern immunology has been built on specific pathogen-free (SPF) mice. Defined model antigens such as ovalbumin and their cognate T cells allowed the field to map the signaling pathways that govern T cell activation, tolerance, and immunity to bacteria, viruses, and tumors; the value of that body of work is beyond dispute. SPF housing was adopted deliberately to protect colonies from infection-associated mortality and to protect the personnel who work with them. In doing so, however, it also removed the microbial, viral, and parasitic exposures that shape immune systems in the wild and in humans. The consequence is now widely recognized: the immune landscape of a laboratory mouse resembles that of a human neonate more closely than that of an adult. Nowhere does this matter more than at mucosal surfaces, where environmental and commensal microbes continuously instruct regulatory T cell differentiation and barrier immunity.This Research Topic asks what is gained when those exposures are restored. Over the past decade, a range of “wilded” or “re-wilded” systems (pet-store co-housing, wildling mice reconstituted with natural microbiota, wild-caught and outdoor-housed colonies, sequential-infection models, and dietary or soil-derived exposures) has converged on a common observation: they model mouse-to-human translation better than SPF animals do. Alongside humanized models, these “dirty” systems offer a route to identify new targets and cellular pathways, stress-test preclinical findings obtained under SPF conditions, and determine how environmental microbiota, helminths, viruses, and diet jointly set the threshold between mucosal tolerance and inflammation. Recent work also indicates that generating such models does not need to be prohibitively difficult or expensive, provided appropriate biosecurity is maintained. Our goal is to bring the model systems and mucosal immunology communities together to define what these platforms have already delivered, where they mislead, and how they can be standardized sufficiently to enter the routine preclinical pipeline.We welcome contributions addressing, but not limited to: • Design, husbandry, biosecurity, and cost of re-wilded, wildling, wild-caught, and co-housing models • Environmental and commensal microbiota as drivers of regulatory T cell differentiation and mucosal tolerance • Helminth, viral, and polymicrobial exposure in barrier immunity • Diet and soil-derived exposures as modifiers of immune development • Head-to-head comparisons of SPF, re-wilded, and humanized models in the same disease setting • Applications to inflammatory bowel disease, allergy, autoimmunity, infection, and cancer immunotherapy • Wild and free-living animal immunology as a benchmark for laboratory-derived findings • Reproducibility, standardization, and reporting standards for non-SPF colonies • Ethical, regulatory, biosafety, and animal welfare considerations for non-SPF facilitiesWe invite Original Research, Reviews, Mini-Reviews, Methods, Perspectives, Opinions, and Brief Research Reports. The topic editors declare no conflict of interest Topic editors: Michal Kuczma, Chunhua Yang, Hussein Sultan, Lukasz Wojciech Source: https://www.frontiersin.org/research-topics/86123/from-dirty-microbiota-to-immune-tolerance-regulatory-t-cells-and-anti-inflammatory-networks-in-re-wilded-and-humanized-animal-models