B cells secrete eotaxin-1 in human inflammatory bowel disease.

Abstract

BACKGROUND:

Our previous studies have demonstrated that B cells in human inflammatory bowel disease (IBD) are highly activated and produce copious amounts of chemokines. Here, we showed that B cells produce eotaxin-1, a selective chemokine for acute eosinophilia. Increased levels of activated eosinophils have been found in the intestinal mucosa in patients with IBD, but their role(s) and the regulation of their migration patterns remain poorly defined.

METHODS:

To determine how B-cell secretion of eotaxin-1 influences eosinophil activation and migration, we performed immunoepidemiological approaches coupled with in vitro studies. B cells and eosinophils from patients with Crohn's disease and ulcerative colitis were isolated, and responses to Toll-like receptor ligands (TLR) were measured and assessed for the relationship with clinical disease.

RESULTS:

Eotaxin-1 from recirculating B cells, and TLR ligands, regulated eosinophil homing mechanisms in IBD. B cells stimulated with hypo-acylated lipopolysaccharide (LPS) produced copious amounts of eotaxin-1, which influenced eosinophil activation profiles in the bloodstream. We also found that hexa-acylated LPS, such Escherichia coli LPS, directly activated TLR2-expressing and TLR4-expressing eosinophils from patients with IBD to express a different repertoire of mucosal homing receptors, namely CCR9 and CCR10. Whereas B-cell production of eotaxin-1 was correlated with reduced disease activity, eosinophil activation by hexa-acylated LPS was associated with increased disease activity.

CONCLUSIONS:

These results suggest that systemic TLR ligands influence eosinophil migration patterns, both directly and indirectly, through B cells. Our report uncovers unexpected mechanisms of cross talk between certain immune cells that shed new light on IBD immunology.

• Authors: Mian Qasim Rehman, Dominic Beal, YanMei Liang, Ansu Noronha, Harland Winter, Francis A Farraye, Lisa Ganley-Leal
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 19 Issue 5 Pg. 922-33 (Apr 2013) ISSN: 1536-4844 [Electronic] England
• PMID: 23511032 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL11
• Cytokines
• Lipopolysaccharides
• Toll-Like Receptors

Topics

• Adolescent
• B-Lymphocytes (immunology, metabolism, pathology)
• Case-Control Studies
• Cells, Cultured
• Chemokine CCL11 (metabolism)
• Chemotaxis
• Child
• Cohort Studies
• Colitis, Ulcerative (immunology, metabolism, pathology)
• Crohn Disease (immunology, metabolism, pathology)
• Cytokines (metabolism)
• Eosinophils (immunology, metabolism, pathology)
• Humans
• Leukocytes, Mononuclear (immunology, metabolism, pathology)
• Lipopolysaccharides (pharmacology)
• Surveys and Questionnaires
• Toll-Like Receptors (metabolism)