TY - JOUR
T1 - An alternatively spliced CXCL16 isoform expressed by dendritic cells is a secreted chemoattractant for CXCR6+ cells
AU - Van Der Voort, Robbert
AU - Verweij, Viviènne
AU - De Witte, Theo M.
AU - Lasonder, Edwin
AU - Adema, Gosse J.
AU - Dolstra, Harry
N1 - Funding information: This work was supported by the Dutch Cancer Society (grants KUN 99-1947 and KUN 2007-3752). We thank R. Woestenenkand J. van Velzen for cell sorting, Dr. T. Shimaoka (Tokyo, Japan) for generously providing L1.2 transfectants, and Dr. Angelique Rops for technical assistance.
PY - 2010/6/1
Y1 - 2010/6/1
N2 - DC are professional APCs that initiate and regulate adaptive immune responses by interacting with naïve and memory T cells. Chemokines released by DC play an essential role in T cell recruitment and in the maintenance of antigen-specific T cell-DC conjugates. Here, we characterized the expression of the T cell-attracting chemokine CXCL16 by murine DC. We demonstrate that through alternative RNA splicing, DC not only express the previously characterized transmembrane CXCL16 isoform, which can be cleaved from the cell surface, but also a novel isoform lacking the transmembrane and cytoplasmic domains. Transfection of HEK293 cells shows that this novel isoform, termed CXCL16v, is not expressed on the cell membrane but is secreted as a protein of ∼10 kDa. Quantitative PCR demonstrates that CXCL16v is broadly expressed in lymphoid and nonlymphoid tissues resembling the tissue distribution of DC. Indeed, CXCL16v mRNA is expressed significantly by spleen DC and BM-DC. Moreover, we show that mature DC have increased CXCL16v mRNA levels and express transmembrane and soluble CXCL16 proteins. Finally, we show that CXCL16v specifically attracts cells expressing the chemokine receptor CXCR6. Our data demonstrate that mature DC express secreted, transmembrane, and cleaved CXCL16 isoforms to recruit and communicate efficiently with CXCR6+ lymphoid cells.
AB - DC are professional APCs that initiate and regulate adaptive immune responses by interacting with naïve and memory T cells. Chemokines released by DC play an essential role in T cell recruitment and in the maintenance of antigen-specific T cell-DC conjugates. Here, we characterized the expression of the T cell-attracting chemokine CXCL16 by murine DC. We demonstrate that through alternative RNA splicing, DC not only express the previously characterized transmembrane CXCL16 isoform, which can be cleaved from the cell surface, but also a novel isoform lacking the transmembrane and cytoplasmic domains. Transfection of HEK293 cells shows that this novel isoform, termed CXCL16v, is not expressed on the cell membrane but is secreted as a protein of ∼10 kDa. Quantitative PCR demonstrates that CXCL16v is broadly expressed in lymphoid and nonlymphoid tissues resembling the tissue distribution of DC. Indeed, CXCL16v mRNA is expressed significantly by spleen DC and BM-DC. Moreover, we show that mature DC have increased CXCL16v mRNA levels and express transmembrane and soluble CXCL16 proteins. Finally, we show that CXCL16v specifically attracts cells expressing the chemokine receptor CXCR6. Our data demonstrate that mature DC express secreted, transmembrane, and cleaved CXCL16 isoforms to recruit and communicate efficiently with CXCR6+ lymphoid cells.
KW - Chemokines
KW - Mouse
UR - http://www.scopus.com/inward/record.url?scp=77954003833&partnerID=8YFLogxK
U2 - 10.1189/jlb.0709482
DO - 10.1189/jlb.0709482
M3 - Article
C2 - 20181724
AN - SCOPUS:77954003833
VL - 87
SP - 1029
EP - 1039
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -