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Exploring plasma-cell role in mucosal healing

Project description

The role of antibody-producing immune cells in gut healing

Inflammatory bowel disease is a chronic condition characterised by recurring intestinal inflammation that progressively damages the gut lining. Current therapies focus on suppressing inflammation, but many patients relapse or require surgery. Restoring the integrity of the intestinal barrier, a process called mucosal healing, offers a promising alternative strategy for achieving sustained remission. With the support of the Marie Skłodowska-Curie Actions programme, the PLASMA-HEAL project investigates how antibody-producing immune cells, called plasma cells that accumulate during intestinal inflammation, regulate epithelial regeneration. Researchers will utilise organoid models, animal studies and spatial omics technologies in patient samples to determine how plasma cells interact with intestinal stem cells. The project is expected to uncover new therapeutic targets for inflammatory bowel disease.

Objective

Disruption of the intestinal barrier can lead to microbiota translocation and uncontrolled immune activation against the commensal microbiota, a hallmark of inflammatory bowel disease (IBD). Current therapies aim to suppress inflammation, but their effectiveness is limited. Consequently, many patients relapse or progress to surgical bowel resection, underscoring the urgent need for alternative therapeutic strategies. A promising approach is to focus on mucosal healing, which restores barrier integrity and provides sustained remission independent of classic immunosuppression. Mucosal healing relies on the continuous proliferation and differentiation of intestinal stem cells (ISCs) into all epithelial cell types. My host lab is at the forefront of this paradigm. Their recent work revealed a detrimental role of B cells in disrupting stromal–ISC crosstalk, essential for epithelial regeneration. Moreover, plasma cells (PCs)—the antibody-producing progeny of B cells—are emerging therapeutic targets in IBD, as certain populations increase during intestinal inflammation. However, whether PCs play a role in mucosal healing remains unknown. In PLASMA-HEAL, I will combine loss- and gain-of-function approaches, such as in vivo PC depletion and in vitro organoid co-cultures, to determine the role of PCs in intestinal healing. Using a unique prospective cohort of IBD patients and state-of-the-art spatial-omics technologies (spatial transcriptomics, metatranscriptomics, V(D)J, proteomics), I will translate these studies to the human setting. Thus, I will test the hypothesis that PCs critically regulate epithelial regeneration and mucosal healing in IBD. I aim to uncover novel mechanisms of PC–epithelial crosstalk with direct translational implications for IBD therapy. My ultimate goal is to provide fundamental insights into IBD pathogenesis and inform the development of therapies for sustained remission and resection-free survival.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

KAROLINSKA INSTITUTET
Net EU contribution
€ 236 340,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden
Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data