title: Intrarectal immunization and IgA antibody-secreting cell homing to the small intestine.
abstract: According to the current paradigm, lymphocyte homing to the small intestine requires the expression of two tissue-specific homing receptors, the integrin α4β7 and the CCL25 receptor CCR9. In this study, we investigated the organ distribution and the homing molecule expression of IgA Ab-secreting cells (ASCs) induced by intrarectal immunization with a particulate Ag, in comparison with other mucosal immunization routes. Intrarectal immunization induces gut-homing IgA ASCs that localize not only in the colon but also in the small intestine, although they are not responsive to CCL25, unlike IgA ASCs induced by oral immunization. The mucosal epithelial chemokine CCL28, known to attract all IgA ASCs, does not compensate for the lack of CCL25 responsiveness, because the number of Ag-specific cells is not decreased in the gut of CCR10-deficient mice immunized by the intrarectal route. However, Ag-specific IgA ASCs induced by intrarectal immunization express the integrin α4β7, and their number is considerably decreased in the gut of β7-deficient mice immunized by the intrarectal route, indicating that α4β7 enables these cells to migrate into the small intestine, even without CCL25 responsiveness. In contrast, IgA ASCs induced by intranasal immunization express low α4β7 levels and are usually excluded from the gut. Paradoxically, after intranasal immunization, Ag-specific IgA ASCs are significantly increased in the small intestine of β7-deficient mice, demonstrating that lymphocyte homing is a competitive process and that integrin α4β7 determines not only the intestinal tropism of IgA ASCs elicited in GALTs but also the intestinal exclusion of lymphocytes primed in other inductive sites.
authors.affiliation: Laboratoire de Virologie et Centre National de Référence des Virus Entériques, Centre Hospitalier Universitaire de Dijon, 21070 Dijon Cedex, France. Davide.Agnello@u-bourgogne.fr
authors.forename: Davide
authors.initials: D
authors.lastname: Agnello
authors.forename: Damien
authors.initials: D
authors.lastname: Denimal
authors.forename: Amandine
authors.initials: A
authors.lastname: Lavaux
authors.forename: Leslie
authors.initials: L
authors.lastname: Blondeau-Germe
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Norma P
authors.initials: NP
authors.lastname: Gerard
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Pierre
authors.initials: P
authors.lastname: Pothier
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism; D005260:Female; D007114:Immunization / Q000379:methods; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009088:Mucoproteins; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D054447:Receptors, CCR10 / Q000276:immunology / Q000378:metabolism
chemical_list: C491541:Ccl25 protein, mouse; C511142:Ccl28 protein, mouse; C515707:Ccr10 protein, mouse; D015815:Cell Adhesion Molecules; D019742:Chemokines, CC; D007070:Immunoglobulin A; D016023:Integrins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D054447:Receptors, CCR10; C071777:integrin alpha4beta7