[PLASMA-HEAL] Exploring plasma-cell role in mucosal healing
Ente: EC
Scadenza: 2029-07-31
Importo max: 236.340 EUR
Paese: EU
Descrizione
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.
Settori: Horizon Europe Topics
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