The role of mucosal barrier function in the initiation of intestinal inflammation

Inflammatory bowel diseases (IBD) are characterized by severe chronic intestinal inflammation bearing huge impact on the quality of life

Incidence is high and escalating, and current treatments lack in efficacy and safety. Our overall aim is to elucidate mechanisms of epithelial barrier function, its role in interacting with commensal bacteria, and how this communication can be converted to the induction of IBD.

The studies will be based on our specific expertise and unique methodology (micro systems for studies of gut physiology in endoscopic biopsies; availability to inflamed and normal human intestinal mucosa), complemented with know-how from international and national partners to guarantee proficiency in all details. Recent original findings from our laboratory have demonstrated neuropeptide-releasing eosinophils as a previously missing link in the regulation of the epithelial barrier in ulcerative colitis. The importance of the follicle-associated epithelium (FAE) in Crohn¿s disease has also been established.

In the planned projects we anticipate providing novel data on neuro-immune interaction with gut microbiota and probiotics at the frontline, i.e. the intestinal barrier (including FAE, mast cells, and eosinophils) during inflammation and stress. We will thereby increase the understanding of crucial steps in the pathogenesis of IBD and disease relapse, ultimately leading to novel therapeutic approaches for these debilitating diseases.

JohanDS-fogrupp

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2022

Luiza Moraes Holst, Jonas Halfvarson, Marie Carlson, Charlotte Hedin, Robert Kruse, Carl Mårten Lindqvist, Daniel Bergemalm, Sven Almér, Francesca Bresso, Maria Ling Lundström, Dirk Repsilber, Mauro D'Amato, Åsa Keita, Henrik Hjortswang, Johan D Söderholm, Johanna Sundin, Hans Törnblom, Magnus Simrén, Hans Strid, Maria K. Magnusson, Lena Öhman (2022) Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis Clinical and Experimental Gastroenterology, Vol. 15, p. 129-144 Continue to DOI
Efthymia Kokkinou, Ram Vinay Pandey, Luca Mazzurana, Irene Gutierrez-Perez, Christopher Andrew Tibbitt, Whitney Weigel, Tea Soini, Anna Carrasco, Anna Rao, Maho Nagasawa, Suzanne M. Bal, Mattias Jangard, Danielle Friberg, Ulrik Lindforss, Caroline Nordenvall, Malin Ljunggren, Staffan Haapaniemi, Åsa Keita, Johan D Söderholm, Charlotte Hedin, Hergen Spits, Yenan T. Bryceson, Jenny Mjosberg (2022) CD45RA(+)CD62L(-) ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs Science immunology, Vol. 7 Continue to DOI

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