CD4+CD3- cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5.
CD4+CD3- cells are the predominant hematopoietic cells found in mouse fetal intestine. We prove their role as Peyer's patch (PP)-inducing cells by transfer into neonatal PP-deficient mice. To test the requirement of chemokines and adhesion molecules in induction of PP, we studied mice deficient in CXCR5 and/or alpha4beta1 integrin-mediated adhesion. CXCR5-/- mice have CD4+CD3- cells, which are inefficient in inducing PP formation. We show here that CXCR5/CXCL13 signaling activates alpha4beta1 integrin on CD4+CD3- cells. Blocking of beta1 integrin or VCAM-1, the ligand of alpha4beta1 integrin, inhibits PP formation. This study demonstrates the link between chemokine receptors and adhesion molecules that regulates stromal/hematopoietic cell interaction leading to PP formation.
D019264:Adoptive Transfer; D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology* / Q000637:transplantation; D002448:Cell Adhesion; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000502:physiology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D009024:Morphogenesis; D010581:Peyer's Patches / Q000254:growth & development*; D011828:Radiation Chimera; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D017252:CD3 Complex; C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D039041:Integrin alpha4beta1; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D019010:Vascular Cell Adhesion Molecule-1