학술논문

CD47-deficient mice have decreased production of intestinal IgA following oral immunization but a maintained capacity to induce oral tolerance.
Document Type
Article
Source
Immunology. Mar2012, Vol. 135 Issue 3, p236-244. 9p. 1 Chart, 5 Graphs.
Subject
*IMMUNOGLOBULIN A
*LABORATORY mice
*INTESTINAL secretion
*IMMUNIZATION
*BIOCOMPATIBILITY
*GENE expression
*LYMPHOID tissue
*CELLULAR signal transduction
Language
ISSN
0019-2805
Abstract
Summary 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. [ABSTRACT FROM AUTHOR]