Children's immunology, what can we learn from animal studies (3): Impaired mucosal immunity in the gut by 2,3,7,8-tetraclorodibenzo-p-dioxin (TCDD): a possible role for allergic sensitization.
We have recently reported breakdown of mucosal immunity in the gut by tetraclorodibenzo-p-dioxin (TCDD). That is, single oral administration of low dose 2,3,7,8-TCDD resulted in a marked decrease in IgA secretion in AhR-dependent manner and impaired oral tolerance in the gut. In the present study, we found TCDD exposure by breast feeding also resulted in decreased level of IgA in the gut. Ig production by B cells by LPS stimulation was not affected by TCDD administration. Instead, particular chemokine receptor expression on B1 cells, a major cell source for intestinal IgA antibody, was decreased in mice treated with TCDD. In consistence with this observation, B1, but not B2 cells from TCDD treated mice showed impaired chemotaxis towards B lymphocyte chemokine (BLC)/CXCL13. In contrast, chemotaxis of intestinal dendritic cells (DCs) towards secondary lymphoid-tissue chemokine (SLC)/CXCL19 was not impaired in mice treated with TCDD. Furthermore, there was no change in the number and profile of intestinal microflora in TCDD-treated mice. These results indicate that TCDD exposure by breast feeding results in breakdown of intestinal mucosal immunity of pups and that it may be attributed in part to impaired B1 cell migration from the peritoneal cavity to intestinal mucosa.
Ishikawa
Sho
S
Dept. of Molecular Preventive Medicine, Graduate School of Medicine, The Univ. of Tokyo, Japan. yamasho@m.u-tokyo.ac.jp
D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000276:immunology*; D011247:Pregnancy; D019707:Receptors, Chemokine / Q000378:metabolism
D054382:Chemokine CXCL13; D004785:Environmental Pollutants; D007070:Immunoglobulin A; D000072317:Polychlorinated Dibenzodioxins; D019707:Receptors, Chemokine