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

Tools

Item Type:	Article
Title:	ST6GAL1 promotes IBD B cell recruitment to the inflamed colon in a CD22-dependent mechanism
Creators Name:	Liu, Li-Juan, Müller, Tanja M., Dedden, Mark, Schramm, Sebastian, Leppkes, Moritz, Atreya, Raja, Atreya, Imke, Neurath, Markus F. and Zundler, Sebastian
Abstract:	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 recruitment into the inflamed gut mucosa. This pathway might be a novel target to interfere with B lineage cell homing and local auto-antibody production.
Keywords:	Gut Homing, B Cells, IBD
Source:	Journal of Crohn's & Colitis
ISSN:	1873-9946
Publisher:	Oxford University Press
Volume:	19
Number:	7
Page Range:	jjaf097
Date:	July 2025
Additional Information:	Leif S.-H. Ludwig and Ashley Sanders are members of the TRR241 IBDome consortium.
Official Publication:	https://doi.org/10.1093/ecco-jcc/jjaf097
PubMed:	View item in PubMed

Repository Staff Only: item control page