ST6GAL1 promotes IBD B cell recruitment to the inflamed colon in a CD22-dependent mechanism

作者：Lijuan Liu, Tanja M Müller, Mark Dedden, Sebastian Schramm, Moritz Leppkes, Raja Atreya, Imke Atreya, Imke Atreya, Raja Atreya, Petra Bacher, Christoph Becker, Christian Bojarski, Nathalie Britzen-Laurent, Caroline Bosch-Voskens, Hyun-Dong Chang, Andreas Diefenbach, Claudia Günther, Ahmed N Hegazy, Kai Hildner, Christoph Sn Klose, Kristina Koop, Susanne Krug, Anja A Kühl, Moritz Leppkes, Rocío López-Posadas, Leif S-H Ludwig, Clemens Neufert, Markus F. Neurath, Jay Patankar, Christina Plattner, Magdalena Prüß, Andreas Radbruch, Chiara Romagnani, Francesca Ronchi, Ashley Sanders, Alexander Scheffold, Jörg-Dieter Schulzke, Michael Schumann, Sebastian Schürmann, Britta Siegmund, Michael Stürzl, Zlatko Trajanoski, Antigoni Triantafyllopoulou, Maximilian Waldner, Carl Weidinger, Stefan Wirtz, Sebastian Zundler, Markus F. Neurath, Sebastian Zundler · 发表于：Journal of Crohn s and Colitis · 年份：2025 · DOI：10.1093/ecco-jcc/jjaf097 · 被引用次数：2 · 研究领域：Cell Adhesion Molecules Research、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

BACKGROUND AND AIMS: Since the discovery that auto-reactive anti-αvβ6 integrin antibodies are associated with ulcerative colitis, cells from the B cell lineage, especially plasmablasts and plasma cells have increasingly come into the focus of research on inflammatory bowel disease. However, the mechanisms regulating their recruitment from the circulation to the gut remain poorly understood. Here, we explored whether the B cell-specific lectin CD22 interacts with endothelial α2,6-linked sialic acid residues attached by ST6GAL1 to mediate such recruitment in IBD. METHODS: Flow cytometry, transcriptomics, immunofluorescence, dynamic adhesion assays, and in vivo homing assays were employed to study the role of ST6GAL1 and CD22 in regulating B cell trafficking to the inflamed gut. RESULTS: Plasmablasts were relatively reduced in the circulating B cell compartment of patients with IBD. CD22 was expressed on the majority of B cells and plasmablasts. ST6GAL1 was expressed on vessels in the colon and its expression was nominally increased in IBD. The interaction of CD22 with α2,6-linked sialic acids controlled dynamic B cell adhesion in vitro and, consistently, the in vivo gut homing of IBD B cells to the inflamed colon could be blocked by anti-CD22 antibodies in humanized mice. CONCLUSIONS: Our findings suggest that endothelial ST6GAL1 creates a pro-adhesive microenvironment rich in α2,6-sialic acids that engage CD22 on circulating B cells and plasmablasts to promote their recruitmen...