CCL28 (MEC) is increased in human Helicobacter pylori induced gastritis and mediates recruitment of gastric IgA-secreting cells

Department of Microbiology and Immunology, Institute of Biomedicine, and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Box 435, 405 30 Göteborg, Sweden; Department of Surgery, Institute of Medicine, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden

^* To whom correspondence should be addressed. Email: marianne.quiding{at}microbio.gu.se.

	Abstract

Human Helicobacter pylori infection gives rise to an active chronic gastritis and is a major risk factor for development of duodenal ulcer disease and gastric adenocarcinoma. The infection is accompanied by a large accumulation of IgA-secreting cells in the gastric mucosa, and following mucosal immunization only H. pylori infected volunteers mount 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 (MEC) and CCL25 (TECK) in H. pylori infected and uninfected individuals, and the potential of gastric B cell populations to migrate towards these chemokines. Gastric tissue from H. pylori infected individuals contained significantly more CCL28 protein and mRNA compared to 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 towards 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-1). 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 to the large influx of IgA-secreting cells to the gastric mucosa in H. pylori infected individuals.