Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes

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Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes. / Janssens, Rik; Mortier, Anneleen; Boff, Daiane; Ruytinx, Pieter; Gouwy, Mieke; Vantilt, Bo; Larsen, Olav; Daugvilaite, Viktorija; Rosenkilde, Mette M; Parmentier, Marc; Noppen, Sam; Liekens, Sandra; Van Damme, Jo; Struyf, Sofie; Teixeira, Mauro M.; Amaral, Flávio A.; Proost, Paul.

In: Biochemical Pharmacology, Vol. 132, 2017, p. 92-101.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Janssens, R, Mortier, A, Boff, D, Ruytinx, P, Gouwy, M, Vantilt, B, Larsen, O, Daugvilaite, V, Rosenkilde, MM, Parmentier, M, Noppen, S, Liekens, S, Van Damme, J, Struyf, S, Teixeira, MM, Amaral, FA & Proost, P 2017, 'Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes', Biochemical Pharmacology, vol. 132, pp. 92-101. https://doi.org/10.1016/j.bcp.2017.03.009

APA

Janssens, R., Mortier, A., Boff, D., Ruytinx, P., Gouwy, M., Vantilt, B., Larsen, O., Daugvilaite, V., Rosenkilde, M. M., Parmentier, M., Noppen, S., Liekens, S., Van Damme, J., Struyf, S., Teixeira, M. M., Amaral, F. A., & Proost, P. (2017). Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes. Biochemical Pharmacology, 132, 92-101. https://doi.org/10.1016/j.bcp.2017.03.009

Vancouver

Janssens R, Mortier A, Boff D, Ruytinx P, Gouwy M, Vantilt B et al. Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes. Biochemical Pharmacology. 2017;132:92-101. https://doi.org/10.1016/j.bcp.2017.03.009

Author

Janssens, Rik ; Mortier, Anneleen ; Boff, Daiane ; Ruytinx, Pieter ; Gouwy, Mieke ; Vantilt, Bo ; Larsen, Olav ; Daugvilaite, Viktorija ; Rosenkilde, Mette M ; Parmentier, Marc ; Noppen, Sam ; Liekens, Sandra ; Van Damme, Jo ; Struyf, Sofie ; Teixeira, Mauro M. ; Amaral, Flávio A. ; Proost, Paul. / Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes. In: Biochemical Pharmacology. 2017 ; Vol. 132. pp. 92-101.

Bibtex

@article{ead9885647ed46e7a462896d190f0c6e,
title = "Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes",
abstract = "The chemokine CXCL12 or stromal cell-derived factor 1/SDF-1 attracts hematopoietic progenitor cells and mature leukocytes through the G protein-coupled CXC chemokine receptor 4 (CXCR4). In addition, it interacts with atypical chemokine receptor 3 (ACKR3 or CXCR7) and glycosaminoglycans. CXCL12 activity is regulated through posttranslational cleavage by CD26/dipeptidyl peptidase 4 that removes two NH2-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells. CXCL12(3-68) was chemically synthesized de novo for detailed biological characterization. Compared to unmodified CXCL12, CXCL12(3-68) was no longer able to signal through CXCR4 via inositol trisphosphate (IP3), Akt or extracellular signal-regulated kinases 1 and 2 (ERK1/2). Interestingly, the recruitment of β-arrestin 2 to the cell membrane via CXCR4 by CXCL12(3-68) was abolished, whereas a weakened but significant β-arrestin recruitment remained via ACKR3. CXCL12-induced endothelial cell migration and signal transduction was completely abrogated by CD26. Intact CXCL12 hardly induced lymphocyte migration upon intra-articular injection in mice. In contrast, oral treatment of mice with the CD26 inhibitor sitagliptin reduced CD26 activity and CXCL12 cleavage in blood plasma. The potential of CXCL12 to induce intra-articular lymphocyte infiltration was significantly increased in sitagliptin-treated mice and CXCL12(3-68) failed to induce migration under both CD26-inhibiting and non-inhibiting conditions. In conclusion, CD26-cleavage skews CXCL12 towards β-arrestin dependent recruitment through ACKR3 and destroys the CXCR4-mediated lymphocyte chemoattractant properties of CXCL12 in vivo. Hence, pharmacological CD26-blockade in tissues may enhance CXCL12-induced inflammation.",
author = "Rik Janssens and Anneleen Mortier and Daiane Boff and Pieter Ruytinx and Mieke Gouwy and Bo Vantilt and Olav Larsen and Viktorija Daugvilaite and Rosenkilde, {Mette M} and Marc Parmentier and Sam Noppen and Sandra Liekens and {Van Damme}, Jo and Sofie Struyf and Teixeira, {Mauro M.} and Amaral, {Fl{\'a}vio A.} and Paul Proost",
note = "Copyright {\textcopyright} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
doi = "10.1016/j.bcp.2017.03.009",
language = "English",
volume = "132",
pages = "92--101",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes

AU - Janssens, Rik

AU - Mortier, Anneleen

AU - Boff, Daiane

AU - Ruytinx, Pieter

AU - Gouwy, Mieke

AU - Vantilt, Bo

AU - Larsen, Olav

AU - Daugvilaite, Viktorija

AU - Rosenkilde, Mette M

AU - Parmentier, Marc

AU - Noppen, Sam

AU - Liekens, Sandra

AU - Van Damme, Jo

AU - Struyf, Sofie

AU - Teixeira, Mauro M.

AU - Amaral, Flávio A.

AU - Proost, Paul

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017

Y1 - 2017

N2 - The chemokine CXCL12 or stromal cell-derived factor 1/SDF-1 attracts hematopoietic progenitor cells and mature leukocytes through the G protein-coupled CXC chemokine receptor 4 (CXCR4). In addition, it interacts with atypical chemokine receptor 3 (ACKR3 or CXCR7) and glycosaminoglycans. CXCL12 activity is regulated through posttranslational cleavage by CD26/dipeptidyl peptidase 4 that removes two NH2-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells. CXCL12(3-68) was chemically synthesized de novo for detailed biological characterization. Compared to unmodified CXCL12, CXCL12(3-68) was no longer able to signal through CXCR4 via inositol trisphosphate (IP3), Akt or extracellular signal-regulated kinases 1 and 2 (ERK1/2). Interestingly, the recruitment of β-arrestin 2 to the cell membrane via CXCR4 by CXCL12(3-68) was abolished, whereas a weakened but significant β-arrestin recruitment remained via ACKR3. CXCL12-induced endothelial cell migration and signal transduction was completely abrogated by CD26. Intact CXCL12 hardly induced lymphocyte migration upon intra-articular injection in mice. In contrast, oral treatment of mice with the CD26 inhibitor sitagliptin reduced CD26 activity and CXCL12 cleavage in blood plasma. The potential of CXCL12 to induce intra-articular lymphocyte infiltration was significantly increased in sitagliptin-treated mice and CXCL12(3-68) failed to induce migration under both CD26-inhibiting and non-inhibiting conditions. In conclusion, CD26-cleavage skews CXCL12 towards β-arrestin dependent recruitment through ACKR3 and destroys the CXCR4-mediated lymphocyte chemoattractant properties of CXCL12 in vivo. Hence, pharmacological CD26-blockade in tissues may enhance CXCL12-induced inflammation.

AB - The chemokine CXCL12 or stromal cell-derived factor 1/SDF-1 attracts hematopoietic progenitor cells and mature leukocytes through the G protein-coupled CXC chemokine receptor 4 (CXCR4). In addition, it interacts with atypical chemokine receptor 3 (ACKR3 or CXCR7) and glycosaminoglycans. CXCL12 activity is regulated through posttranslational cleavage by CD26/dipeptidyl peptidase 4 that removes two NH2-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells. CXCL12(3-68) was chemically synthesized de novo for detailed biological characterization. Compared to unmodified CXCL12, CXCL12(3-68) was no longer able to signal through CXCR4 via inositol trisphosphate (IP3), Akt or extracellular signal-regulated kinases 1 and 2 (ERK1/2). Interestingly, the recruitment of β-arrestin 2 to the cell membrane via CXCR4 by CXCL12(3-68) was abolished, whereas a weakened but significant β-arrestin recruitment remained via ACKR3. CXCL12-induced endothelial cell migration and signal transduction was completely abrogated by CD26. Intact CXCL12 hardly induced lymphocyte migration upon intra-articular injection in mice. In contrast, oral treatment of mice with the CD26 inhibitor sitagliptin reduced CD26 activity and CXCL12 cleavage in blood plasma. The potential of CXCL12 to induce intra-articular lymphocyte infiltration was significantly increased in sitagliptin-treated mice and CXCL12(3-68) failed to induce migration under both CD26-inhibiting and non-inhibiting conditions. In conclusion, CD26-cleavage skews CXCL12 towards β-arrestin dependent recruitment through ACKR3 and destroys the CXCR4-mediated lymphocyte chemoattractant properties of CXCL12 in vivo. Hence, pharmacological CD26-blockade in tissues may enhance CXCL12-induced inflammation.

U2 - 10.1016/j.bcp.2017.03.009

DO - 10.1016/j.bcp.2017.03.009

M3 - Journal article

C2 - 28322746

VL - 132

SP - 92

EP - 101

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

ER -

ID: 176653023