Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans

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

Standard

Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans. / Ridley, Amanda J.L.; Ou, Yaqing; Karlsson, Richard; Pun, Nabina; Birchenough, Holly L.; Mulholland, Iashia Z.; Birch, Mary L.; MacDonald, Andrew S.; Jowitt, Thomas A.; Lawless, Craig; Miller, Rebecca L.; Dyer, Douglas P.

In: Science Signaling, Vol. 16, No. 810, eadf2537, 2023.

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

Harvard

Ridley, AJL, Ou, Y, Karlsson, R, Pun, N, Birchenough, HL, Mulholland, IZ, Birch, ML, MacDonald, AS, Jowitt, TA, Lawless, C, Miller, RL & Dyer, DP 2023, 'Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans', Science Signaling, vol. 16, no. 810, eadf2537. https://doi.org/10.1126/scisignal.adf2537

APA

Ridley, A. J. L., Ou, Y., Karlsson, R., Pun, N., Birchenough, H. L., Mulholland, I. Z., Birch, M. L., MacDonald, A. S., Jowitt, T. A., Lawless, C., Miller, R. L., & Dyer, D. P. (2023). Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans. Science Signaling, 16(810), [eadf2537]. https://doi.org/10.1126/scisignal.adf2537

Vancouver

Ridley AJL, Ou Y, Karlsson R, Pun N, Birchenough HL, Mulholland IZ et al. Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans. Science Signaling. 2023;16(810). eadf2537. https://doi.org/10.1126/scisignal.adf2537

Author

Ridley, Amanda J.L. ; Ou, Yaqing ; Karlsson, Richard ; Pun, Nabina ; Birchenough, Holly L. ; Mulholland, Iashia Z. ; Birch, Mary L. ; MacDonald, Andrew S. ; Jowitt, Thomas A. ; Lawless, Craig ; Miller, Rebecca L. ; Dyer, Douglas P. / Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans. In: Science Signaling. 2023 ; Vol. 16, No. 810.

Bibtex

@article{0b6b02e469fc4127b5ede03bebfa10e9,
title = "Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans",
abstract = "Chemokine-driven leukocyte recruitment is a key component of the immune response and of various diseases. Therapeutically targeting the chemokine system in inflammatory disease has been unsuccessful, which has been attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies. We analyzed the expression of genes encoding chemokines and their receptors across species, tissues, and diseases. This analysis revealed complex expression patterns such that genes encoding multiple chemokines that mediated recruitment of the same leukocyte type were expressed in the same context, such as the genes encoding the CXCR3 ligands CXCL9, CXCL10, and CXCL11. Through biophysical approaches, we showed that these chemokines differentially interacted with extracellular matrix glycosaminoglycans (ECM GAGs), which was enhanced by sulfation of specific GAGs. Last, in vivo approaches demonstrated that GAG binding was critical for the CXCL9-dependent recruitment of specific T cell subsets but not of others, irrespective of CXCR3 expression. Our data demonstrate that interactions with ECM GAGs regulated whether chemokines were presented on cell surfaces or remained more soluble, thereby affecting chemokine availability and ensuring specificity of chemokine action. Our findings provide a mechanistic understanding of chemokine-mediated immune cell recruitment and identify strategies to target specific chemokines during inflammatory disease.",
author = "Ridley, {Amanda J.L.} and Yaqing Ou and Richard Karlsson and Nabina Pun and Birchenough, {Holly L.} and Mulholland, {Iashia Z.} and Birch, {Mary L.} and MacDonald, {Andrew S.} and Jowitt, {Thomas A.} and Craig Lawless and Miller, {Rebecca L.} and Dyer, {Douglas P.}",
year = "2023",
doi = "10.1126/scisignal.adf2537",
language = "English",
volume = "16",
journal = "Science Signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "810",

}

RIS

TY - JOUR

T1 - Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans

AU - Ridley, Amanda J.L.

AU - Ou, Yaqing

AU - Karlsson, Richard

AU - Pun, Nabina

AU - Birchenough, Holly L.

AU - Mulholland, Iashia Z.

AU - Birch, Mary L.

AU - MacDonald, Andrew S.

AU - Jowitt, Thomas A.

AU - Lawless, Craig

AU - Miller, Rebecca L.

AU - Dyer, Douglas P.

PY - 2023

Y1 - 2023

N2 - Chemokine-driven leukocyte recruitment is a key component of the immune response and of various diseases. Therapeutically targeting the chemokine system in inflammatory disease has been unsuccessful, which has been attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies. We analyzed the expression of genes encoding chemokines and their receptors across species, tissues, and diseases. This analysis revealed complex expression patterns such that genes encoding multiple chemokines that mediated recruitment of the same leukocyte type were expressed in the same context, such as the genes encoding the CXCR3 ligands CXCL9, CXCL10, and CXCL11. Through biophysical approaches, we showed that these chemokines differentially interacted with extracellular matrix glycosaminoglycans (ECM GAGs), which was enhanced by sulfation of specific GAGs. Last, in vivo approaches demonstrated that GAG binding was critical for the CXCL9-dependent recruitment of specific T cell subsets but not of others, irrespective of CXCR3 expression. Our data demonstrate that interactions with ECM GAGs regulated whether chemokines were presented on cell surfaces or remained more soluble, thereby affecting chemokine availability and ensuring specificity of chemokine action. Our findings provide a mechanistic understanding of chemokine-mediated immune cell recruitment and identify strategies to target specific chemokines during inflammatory disease.

AB - Chemokine-driven leukocyte recruitment is a key component of the immune response and of various diseases. Therapeutically targeting the chemokine system in inflammatory disease has been unsuccessful, which has been attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies. We analyzed the expression of genes encoding chemokines and their receptors across species, tissues, and diseases. This analysis revealed complex expression patterns such that genes encoding multiple chemokines that mediated recruitment of the same leukocyte type were expressed in the same context, such as the genes encoding the CXCR3 ligands CXCL9, CXCL10, and CXCL11. Through biophysical approaches, we showed that these chemokines differentially interacted with extracellular matrix glycosaminoglycans (ECM GAGs), which was enhanced by sulfation of specific GAGs. Last, in vivo approaches demonstrated that GAG binding was critical for the CXCL9-dependent recruitment of specific T cell subsets but not of others, irrespective of CXCR3 expression. Our data demonstrate that interactions with ECM GAGs regulated whether chemokines were presented on cell surfaces or remained more soluble, thereby affecting chemokine availability and ensuring specificity of chemokine action. Our findings provide a mechanistic understanding of chemokine-mediated immune cell recruitment and identify strategies to target specific chemokines during inflammatory disease.

U2 - 10.1126/scisignal.adf2537

DO - 10.1126/scisignal.adf2537

M3 - Journal article

C2 - 37934811

AN - SCOPUS:85176427535

VL - 16

JO - Science Signaling

JF - Science Signaling

SN - 1945-0877

IS - 810

M1 - eadf2537

ER -

ID: 373661517