title: CD47-deficient mice have decreased production of intestinal IgA following oral immunization but a maintained capacity to induce oral tolerance.
abstract: Signal regulatory protein α (SIRPα/CD172a), expressed by myeloid cells including CD11b(+)  dendritic cells, interacts with ubiquitously expressed CD47 to mediate cell-cell signalling and therefore, may be pivotal in the development of tolerance or immunity. We show that in mice deficient in CD47 (CD47(-/-) ) the cellularity in gut-associated lymphoid tissues is reduced by 50%. In addition, the frequency of CD11b(+)  CD172a(+)  dendritic cells is significantly reduced in the gut and mesenteric lymph nodes, but not in Peyer's patches. Activation of ovalbumin (OVA)-specific CD4(+)  T cells in the mesenteric lymph nodes after feeding OVA is reduced in CD47(-/-)  mice compared with wild-type however, induction of oral tolerance is maintained. The addition of cholera toxin generated normal serum anti-OVA IgG and IgA titres but resulted in reduced intestinal anti-OVA IgA in CD47(-/-)  mice. Replacing the haematopoietic compartment in CD47(-/-)  mice with wild-type cells restored neither the cellularity in gut-associated lymphoid tissues nor the capacity to produce intestinal anti-OVA IgA following immunization. This study demonstrates that CD47 signalling is dispensable for oral tolerance induction, whereas the expression of CD47 by non-haematopoietic cells is required for intestinal IgA B-cell responses. This suggests that differential CD4 T cell functions control tolerance and enterotoxin-induced IgA immunity in the gut.
authors: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors: Jessica
authors: J
authors: Westlund
authors: Megan
authors: M
authors: Livingston
authors: Linda
authors: L
authors: Fahlén-Yrlid
authors: Per-Arne
authors: PA
authors: Oldenborg
authors: Ulf
authors: U
authors: Yrlid
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism*; D002772:Cholera Toxin / Q000008:administration & dosage; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007422:Intestines / Q000276:immunology*; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology
chemical_list: D051928:CD47 Antigen; C497894:CD47 protein, human; D007070:Immunoglobulin A; D010047:Ovalbumin; D002772:Cholera Toxin