Critical role for CXC chemokine ligand 16 (SR-PSOX) in Th1 response mediated by NKT cells.
The transmembrane chemokine CXCL 16 (CXCL16), which is the same molecule as the scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX), has been shown to mediate chemotaxis and adhesion of CXC chemokine receptor 6-expressing cells such as NKT and activated Th1 cells. We generated SR-PSOX/CXCL16-deficient mice and examined the role of this chemokine in vivo. The mutant mice showed a reduced number of liver NKT cells, and decreased production of IFN-gamma and IL-4 by administration of alpha-galactosylceramide (alphaGalCer). Of note, the alphaGalCer-induced production of IFN-gamma was more severely impaired than the production of IL-4 in SR-PSOX-deficient mice. In this context, SR-PSOX-deficient mice showed impaired sensitivity to alphaGalCer-induced anti-tumor effect mediated by IFN-gamma from NKT cells. NKT cells from wild-type mice showed impaired production of IFN-gamma, but not IL-4, after their culture with alphaGalCer and APCs from mutant mice. Moreover, Propionibacterium acnes-induced in vivo Th1 responses were severely impaired in SR-PSOX-deficient as well as NKT KO mice. Taken together, SR-PSOX/CXCL16 plays an important role in not only the production of IFN-gamma by NKT cells, but also promotion of Th1-inclined immune responses mediated by NKT cells.
Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan.
Takeshi
T
Shimaoka
Ken-ichiro
K
Seino
Noriaki
N
Kume
Manabu
M
Minami
Chiyoko
C
Nishime
Makoto
M
Suematsu
Toru
T
Kita
Masaru
M
Taniguchi
Kouji
K
Matsushima
Shin
S
Yonehara
D000818:Animals; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000235:genetics / Q000502:physiology*; D005699:Galactosylceramides / Q000008:administration & dosage; D016908:Gram-Positive Bacterial Infections / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011425:Propionibacterium acnes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma