Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFkappaB-inducing kinase in stromal cells.
We previously reported that sphingosine 1-phosphate (S1P) regulates peritoneal B-cell trafficking and subsequent intestinal IgA production, but the underlying mechanisms remain obscure. We demonstrate here that nuclear factor kappaB-inducing kinase (NIK) is involved in the regulation of S1P-mediated trafficking of peritoneal B cells. Although peritoneal B cells from NIK-mutated alymphoplasia (aly) mice expressed type 1 S1P receptor (S1P(1)) at comparable levels and demonstrated normal migration toward S1P, aly peritoneal B cells showed decreased sensitivity to FTY720, an S1P(1) modulator. NIK-mutated stromal cells showed decreased levels of adhesion molecules (VCAM-1 and ICAM-1) and increased CXCL13 expressions, leading to impaired ability to support S1P-mediated emigration, but not immigration, of peritoneal B cells. Therefore, aly peritoneal B cells exhibited normal S1P-mediated peritoneal B-cell trafficking from peritoneum to intestine for IgA production when they were transferred into severe combined immunodeficient or wild-type mice. However, S1P-mediated emigration of wild-type B cells from the aly peritoneal cavity was impaired without affecting their immigration from the blood. Further, transfer of wild-type stromal cells into the peritoneum restored S1P-mediated trafficking of aly peritoneal B cells. These findings suggest that NIK in stromal cells has a specific role in the regulation of S1P-mediated trafficking of peritoneal B cells.
Kunisawa
Jun
J
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Gohda
Masashi
M
Kurashima
Yosuke
Y
Ishikawa
Izumi
I
Higuchi
Morio
M
Kiyono
Hiroshi
H
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D054382:Chemokine CXCL13 / Q000032:analysis; D002634:Chemotaxis, Leukocyte; D005260:Female; D008246:Lysophospholipids / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010537:Peritoneum / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D017154:Stromal Cells / Q000201:enzymology*; D000097782:NF-kappaB-Inducing Kinase
D015815:Cell Adhesion Molecules; D054382:Chemokine CXCL13; D008246:Lysophospholipids; D017346:Protein Serine-Threonine Kinases; D013110:Sphingosine; D000097782:NF-kappaB-Inducing Kinase; C486386:Cxcl13 protein, mouse; C060506:sphingosine 1-phosphate