Glial Regulation of Barrier Tissues in Development, Health and Disease

Host

Carlos Minutti, PhD, Immunoregulation Lab 

Venue

Seminar room

Abstract

Inflammatory conditions of the lung and gut are major global cause of mortality and morbidity. Commensurate to their importance, numerous studies have uncovered important contributions of epithelial, immune and stromal cells in inflammatory responses and host defence in symbiosis with the microbiota. Despite such advances, the mechanistic understanding of disease pathogenesis and treatment options for patients are still limited. Thus, the identification of novel cell interactions and mechanisms underlying these diseases is an urgent unmet clinical need.

Barrier organs are densely innervated by intricate networks of nerves and glial cells that are integral to the organisation and function of these tissues. Interactions between peripheral nerves and the immune system play a crucial part in inflammatory responses, tissue repair and host defence against pathogens, however the role of peripheral nerve-associated glial cells in maintaining and restoring the function of barrier organs is still elusive.

Our recent work has uncovered novel immunoregulatory roles for enteric glial cells. Using transcriptomic profiling and gene knock-out strategies, we have discovered that an IFNγ-enteric glia signalling axis is essential for maintaining intestinal immune homeostasis and tissue integrity at steady state. In addition, we found that activation of this axis is required to promote tissue repair following pathogen invasion of the gut. Extending these findings, our molecular analysis of enteric nervous system lineages throughout development has identified a series of tissue context-dependent immune gene modules in enteric glia, suggesting wider roles of these cells in immune regulation of the intestine. Our recent studies have uncovered similarities in the distribution and molecular profiles of enteric and lung glial cells, arguing that peripheral glia represent important regulatory nodes for maintaining and restoring tissue integrity in barrier organs and represent key cellular players in lung and gut inflammatory disease pathogenesis.

Biography

Fränze obtained a PhD in Immunology from Imperial College London. As a postdoctoral fellow, at the Francis Crick Institute, Fränze uncovered novel immunoregulatory functions for enteric glia during intestinal inflammation. Fränze is now group leader at the Kennedy Institute of Rheumatology, University of Oxford. The work in her lab aims to uncover fundamental roles of peripheral glia in barrier tissue immunity 

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Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.