CCL28 is increased in human Helicobacter pylori-induced gastritis and mediates recruitment of gastric immunoglobulin A-secreting cells.
Human Helicobacter pylori infection gives rise to an active chronic gastritis and is a major risk factor for the development of duodenal ulcer disease and gastric adenocarcinoma. The infection is accompanied by a large accumulation of immunoglobulin A (IgA)-secreting cells in the gastric mucosa, and following mucosal immunization only H. pylori-infected volunteers mounted a B-cell response in the gastric mucosa. To identify the signals for recruitment of gastric IgA-secreting cells, we investigated the gastric production of CCL28 (mucosa-associated epithelial chemokine) and CCL25 (thymus-expressed chemokine) in H. pylori-infected and uninfected individuals and the potential of gastric B-cell populations to migrate toward these chemokines. Gastric tissue from H. pylori-infected individuals contained significantly more CCL28 protein and mRNA than that from uninfected individuals, while CCL25 levels remained unchanged. Chemokine-induced migration of gastric lamina propria lymphocytes isolated from patients undergoing gastric resection was then assessed using the Transwell system. IgA-secreting cells and IgA(+) memory B cells from H. pylori-infected tissues migrated toward CCL28 but not CCL25, while the corresponding cells from uninfected patients did not. Furthermore, IgG-secreting cells from H. pylori-infected patients did not migrate to CCL28 but instead to CXCL12 (SDF-1alpha). However, chemokine receptor expression did not correlate to the migratory pattern of the different B-cell populations. These studies are the first to show increased CCL28 production during gastrointestinal infection in humans and provide an explanation for the large influx of IgA-secreting cells to the gastric mucosa in H. pylori-infected individuals.
Hansson
Malin
M
Department of Microbiology and Immunology, Institute of Biomedicine, and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Box 435, 405 30 Göteborg, Sweden.
Hermansson
Michael
M
Svensson
Helena
H
Elfvin
Anders
A
Hansson
Lars-Erik
LE
Johnsson
Erik
E
Sjöling
Asa
A
Quiding-Järbrink
Marianne
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D019742:Chemokines, CC / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation
C108074:CCL25 protein, human; C414047:CCL28 protein, human; D019742:Chemokines, CC; D007071:Immunoglobulin A, Secretory