CXCL16 is a novel mediator of the innate immunity of epidermal keratinocytes

Tohyama, Mikiko; Sayama, Koji; Komatsuzawa, Hitoshi; Hanakawa, Yasushi; Shirakata, Yuji; Dai, Xjuju; Yang, Lüjun; Tokumaru, Sho; Nagai, Hiroshi; Hirakawa, Satoshi; Sugai, Motoyuki; Hashimoto, Koji

doi:10.1093/intimm/dxm083

Cited by 62 publications

(60 citation statements)

References 34 publications

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“…35 Also, it was reported that nonimmune cells such as smooth muscle cells and keratinocytes expressed CXCL16. 34,36 In our experiment, we found that CXCL16 was expressed on the damaged glomerular cells, probably mesangial cells, but not on intact glomerular cells, and the development of glomerulopathy recruited NKT cells into affected kidney, where CXCL16 was expressed.…”

Section: Discussionmentioning

confidence: 56%

“…19 CXCL16 was discovered as a ligand for CXCR6 that is expressed on activated T and NKT cells and is a membranebound chemokine. 33,34 We hypothesized that renal injury mediated by anti-GBM Ab might induce the intraglomerular upregulation of CXCL16. As shown in Figure 5A, CXCL16 was BASIC RESEARCH www.jasn.org expressed evidently by the induction of ecGN regardless of the presence of NKT cells.…”

Section: Discussionmentioning

confidence: 99%

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NKT Cells Inhibit the Development of Experimental Crescentic Glomerulonephritis

Yang

Kim

et al. 2008

Journal of the American Society of Nephrology

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CD1d is an MHC class I-like, ␤2-microglobulin-associated protein, constitutively expressed by antigenpresenting cells and some epithelial cells, which is recognized by NKT cells, a subpopulation of T cells. CD1d-dependent NKT cells confer protection in immune-mediated disorders, but whether these cells modulate the development of glomerulonephritis is unknown. Experimental crescentic glomerulonephritis was induced by administering anti-glomerular basement membrane antibodies to NKT cell-deficient (CD1d Ϫ/Ϫ ) and wild-type mice. Compared with wild-type mice, NKT cell-deficient mice had an accelerated course of glomerulonephritis measured by renal function and crescent formation, and this was abrogated by adoptive transfer of NKT cells. Reconstitution with NKT cells also attenuated intraglomerular expression of TGF-␤1 and decreased phosphorylation of the transcription factors NF-B and IB. Adopted transfer of fluorescence-labeled NKT cells demonstrated their distribution to glomeruli damaged by anti-glomerular basement membrane antibodies but not to the tubulointerstitium. The chemokine CXCL16, which is the ligand for CXCR6 on NKT cells, was upregulated in glomeruli after induction of glomerulonephritis, and NKT cells were present in the same glomeruli. In vitro, NKT cells inhibited LPS-stimulated proliferation of mesangial cells, an affect that was reduced by co-current treatment with an anti-CXCL16 monoclonal antibody. In summary, these findings highlight the regulatory capacity of CD1d-dependent NKT cells in experimental glomerulonephritis and suggest that CXCL16 is involved in the recruitment of these cells to the site of injury.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

NKT Cells Inhibit the Development of Experimental Crescentic Glomerulonephritis

Yang

Kim

et al. 2008

Journal of the American Society of Nephrology

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“…CXCL16 is produced by diverse tissues and cells including dendritic cells (21), lymphocytes (59), vascular smooth muscle cells (55), bone marrow stromal cells (45), tumor cells (40,41), and cardiac tissue (61). Furthermore, SR-PSOX/ CXCL16 is expressed on human endothelial cells and is strongly upregulated by stimulation with proinflammatory cytokines such as TNF-␣ or IFN-␥ (1, 26), mediators associated with inflammatory diseases or ischemia (49,53). Thereby the stimulation of CXCL16 production by TNF-␣ depends on NF-B, p38 MAPK, and protein kinase A (22).…”

Section: Discussionmentioning

confidence: 99%

Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX

Borst

Abed²,

Alesutan³

et al. 2012

American Journal of Physiology-Cell Physiology

222

215

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Suicidal death of erythrocytes, or eryptosis, is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Eryptosis is triggered by increase of cytosolic Ca2+activity, which may result from treatment with the Ca2+ionophore ionomycin or from energy depletion by removal of glucose. The present study tested the hypothesis that phosphatidylserine exposure at the erythrocyte surface fosters adherence to endothelial cells of the vascular wall under flow conditions at arterial shear rates and that binding of eryptotic cells to endothelial cells is mediated by the transmembrane CXC chemokine ligand 16 (CXCL16). To this end, human erythrocytes were exposed to energy depletion (for 48 h) or treated with the Ca2+ionophore ionomycin (1 μM for 30 min). Phosphatidylserine exposure was quantified utilizing annexin-V binding, cell volume was estimated from forward scatter in FACS analysis, and erythrocyte adhesion to human vascular endothelial cells (HUVEC) was determined in a flow chamber model. As a result, both, ionomycin and glucose depletion, triggered eryptosis and enhanced the percentage of erythrocytes adhering to HUVEC under flow conditions at arterial shear rates. The adhesion was significantly blunted in the presence of erythrocyte phosphatidylserine-coating annexin-V (5 μl/ml), of a neutralizing antibody against endothelial CXCL16 (4 μg/ml), and following silencing of endothelial CXCL16 with small interfering RNA. The present observations demonstrate that eryptotic erythrocytes adhere to endothelial cells of the vascular wall in part by interaction of phosphatidylserine exposed at the erythrocyte surface with endothelial CXCL16.

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“…CXCL16 is produced by several cell types including dendritic cells (21), lymphocytes (56), vascular smooth muscle cells (52), bone marrow stromal cells (40), tumor cells (35,36), and cardiac tissue (58). SR-PSOX/CXCL16 expression in endothelial cells is upregulated by proinflammatory cytokines, such as TNF-␣ or IFN-␥ (1,25), known mediators of inflammation and ischemia (46,50). TNF␣ stimulates CXCL16 production via a signaling cascade involving NF-B, p38 MAPK, and protein kinase A (22).…”

Section: Discussionmentioning

confidence: 99%

Sphingomyelinase-induced adhesion of eryptotic erythrocytes to endothelial cells

Abed

Towhid

Mia

et al. 2012

American Journal of Physiology-Cell Physiology

141

101

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Eryptosis, the suicidal erythrocyte death, leads to cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes adhere to the vascular wall by binding of phosphatidylserine to the CXC chemokine ligand 16 (CXCL16). Stimulators of eryptosis include increased cytosolic Ca 2ϩ activity, energy depletion, and activation of ceramide-producing sphingomyelinase. The present study explored whether sphingomyelinase triggers erythrocyte adhesion to endothelial cells. To this end, human erythrocytes were exposed for 6 h to bacterial sphingomyelinase (1-10 mU/ml) and phosphatidylserine exposure was estimated from fluorescent annexin-V-binding, cell volume from forward scatter in FACS-analysis, erythrocyte adhesion to human umbilical vein endothelial cells (HUVEC) from trapping of labeled erythrocytes in a flow chamber under flow conditions at arterial shear rates, and CXCL16 protein abundance utilizing Western blotting and FACS analysis of fluorescent antibody binding. As a result, sphingomyelinase (Ն1 mU/ml) triggered cell shrinkage, phosphatidylserine exposure and erythrocyte adhesion to HUVEC, effects blunted by Ca 2ϩ removal. Adhesion was significantly blunted by phosphatidylserine-coating annexin-V (5 l/ml), following addition of neutralizing antibodies against endothelial CXCL16 (4 g/ml) and following silencing of the CXCL16 gene with small interfering RNA. Pretreatment of HUVEC with sphingomyelinase upregulated CXCL16 protein abundance. Six hours pretreatment of HUVEC with sphingomyelinase (10 mU/ml) or C6-ceramide (50 M) augmented erythrocyte adhesion following a 30-min treatment with Ca 2ϩ ionophore ionomycin (1 M) or following energy depletion by 48-h glucose removal. Thus exposure to sphingomyelinase or C6-ceramide triggers eryptosis followed by phosphatidylserine-and CXCL16-sensitive adhesion of eryptotic erythrocytes to HUVEC.

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CXCL16 is a novel mediator of the innate immunity of epidermal keratinocytes

Cited by 62 publications

References 34 publications

NKT Cells Inhibit the Development of Experimental Crescentic Glomerulonephritis

NKT Cells Inhibit the Development of Experimental Crescentic Glomerulonephritis

Dynamic adhesion of eryptotic erythrocytes to endothelial cells via CXCL16/SR-PSOX

Sphingomyelinase-induced adhesion of eryptotic erythrocytes to endothelial cells

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