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.
Article first published online 18 March 2013
*Section of Infectious Disease, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
†Department of Pathology, Boston University School of Medicine, Boston, Massachusetts
‡Section of Gastroenterology, Boston Medical Center, Boston, Massachusetts
§Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Boston, Massachusetts.
Reprints: Lisa Ganley-Leal, PhD, Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston Medical Center, 650 Albany Street, Room 630, Boston, MA 02118 (e-mail: email@example.com).
This study was supported by the Broad Medical Research Program of the Broad Foundation, a Department of Medicine CTSI Pilot Award 1ULIRR025771, and the Evans Medical Foundation Blood Microbiome ARC.
The authors have no conflicts of interest to disclose.
Received July 27, 2012
Accepted July 31, 2012