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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Nyckelord

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

antibody responses

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)