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CD47-deficient mice have decreased production of intestinal IgA following oral immunization but a maintained capacity to induce oral tolerance.

Artikel i vetenskaplig tidskrift
Författare Jessica Westlund
Megan Livingston
Linda Fahlén-Yrlid
Per-Arne Oldenborg
Ulf Yrlid
Publicerad i Immunology
Volym 135
Nummer/häfte 3
Sidor 236-44
ISSN 1365-2567
Publiceringsår 2012
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 236-44
Språk en
Länkar dx.doi.org/10.1111/j.1365-2567.2011...
Ämnesord Administration, Oral, Animals, Antigens, CD47, genetics, metabolism, CD4-Positive T-Lymphocytes, immunology, Cholera Toxin, administration & dosage, Dendritic Cells, classification, immunology, Immune Tolerance, Immunity, Mucosal, Immunization, Immunoglobulin A, biosynthesis, Intestines, immunology, Lymphocyte Activation, Lymphoid Tissue, immunology, Mice, Mice, Inbred BALB C, Mice, Knockout, Ovalbumin, administration & dosage, immunology, Peyer's Patches, immunology
Ämneskategorier Immunologi inom det medicinska området, Immunbiologi

Sammanfattning

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.

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