About this Research Topic

Background

The gut plays a key role in the development and training of the immune system. It is the largest mucosal surface in the body in contact with the most complex community of organisms, the microbiota. Thus, it harbors the strongest immune compartment of the body. The relevance of the gut in the regulation of the organisms' health, and in particular of the immune system, has been increasingly recognized in recent years. Both, the innate and adaptive immune arms can be impacted by alterations in intestinal homeostasis. However, the specific mechanisms that connect those changes in the gut's local environment, with their impact at distant locations, such as the brain, joints, metabolic tissues, etc; are far from being understood. Elucidating these pathways, which can lead to complex immune pathologies, is essential for defining their aetiology, progression, and avenues for successful therapeutic interventions.

The gut-immune axis is key to bridging host genetic susceptibility and environmental factors in immune-mediated conditions, as proposed by the "leaky gut syndrome" leading to systemic endotoxemia. Studies report that pathology-associated dysbiosis and the "hygiene hypothesis" underlie many autoinflammatory conditions. However, whilst numerous associations with the gut-immune axis have been suggested, few pathological mechanisms have been established. Unraveling the mechanism by which the gut influences the immune system is essential to improving our understanding of the aetiology of autoinflammatory pathologies and opening the door to potential avenues of therapeutic intervention. Given the complexity of the gut-immune axis, the insight from omics studies is required to establish such associations:

- Functional genomic studies could root autoimmune pathologies in the gut.
- Studying the immune repertoire, which offers a fingerprint of past antigenic exposure and fitness of the immune system, could address connections between the gut and adaptive immunity.
- Innate immune training, the recently defined “memory” of the innate immune system, can be unraveled by epigenetic studies, being potentially shaped by many of the gut’s inhabitants.

The scope of this research topic is to refine our understanding of the role of the gut in shaping the immune system and its association with autoinflammatory pathologies. It will pay special attention to mechanistic studies and insights from omics technologies. E.g.:

- Functional genomic studies linking the aetiology of inflammatory pathologies and the gut.
- Immune repertoire characterization, antigen screening and follow-up studies.
- Innate immune training and epigenetic fingerprints of past events originated in the gut.
- Cell tracking studies connecting immune events originated in the gut with distant disease locations.
- Proof-of-concept immunological and therapeutic interventions targeting the gut-immune axis.

Keywords: Gut, inflammation, functional genomics, immune repertoire, innate immune training, microbiome, intestinal homeostasis, leaky gut, hygiene hypothesis, immunomodulation, immune trafficking

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