IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30467-5.html
   My bibliography  Save this article

Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury

Author

Listed:
  • Isaac Francos-Quijorna

    (Institute of Psychiatry, Psychology & Neuroscience
    Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM))

  • Marina Sánchez-Petidier

    (Prince Felipe Research Center, Carrer d´Eduardo Primo Yúfera 3)

  • Emily R. Burnside

    (Institute of Psychiatry, Psychology & Neuroscience
    German Center for Neurodegenerative Diseases (DZNE))

  • Smaranda R. Badea

    (Institute of Psychiatry, Psychology & Neuroscience)

  • Abel Torres-Espin

    (University of California San Francisco)

  • Lucy Marshall

    (Institute of Psychiatry, Psychology & Neuroscience)

  • Fred Winter

    (Royal Netherlands Academy of Sciences)

  • Joost Verhaagen

    (Royal Netherlands Academy of Sciences
    Vrije Universiteit Amsterdam)

  • Victoria Moreno-Manzano

    (Prince Felipe Research Center, Carrer d´Eduardo Primo Yúfera 3)

  • Elizabeth J. Bradbury

    (Institute of Psychiatry, Psychology & Neuroscience)

Abstract

Chondroitin sulfate proteoglycans (CSPGs) act as potent inhibitors of axonal growth and neuroplasticity after spinal cord injury (SCI). Here we reveal that CSPGs also play a critical role in preventing inflammation resolution by blocking the conversion of pro-inflammatory immune cells to a pro-repair phenotype in rodent models of SCI. We demonstrate that enzymatic digestion of CSPG glycosaminoglycans enhances immune cell clearance and reduces pro-inflammatory protein and gene expression profiles at key resolution time points. Analysis of phenotypically distinct immune cell clusters revealed CSPG-mediated modulation of macrophage and microglial subtypes which, together with T lymphocyte infiltration and composition changes, suggests a role for CSPGs in modulating both innate and adaptive immune responses after SCI. Mechanistically, CSPG activation of a pro-inflammatory phenotype in pro-repair immune cells was found to be TLR4-dependent, identifying TLR4 signalling as a key driver of CSPG-mediated immune modulation. These findings establish CSPGs as critical mediators of inflammation resolution failure after SCI in rodents, which leads to prolonged inflammatory pathology and irreversible tissue destruction.

Suggested Citation

  • Isaac Francos-Quijorna & Marina Sánchez-Petidier & Emily R. Burnside & Smaranda R. Badea & Abel Torres-Espin & Lucy Marshall & Fred Winter & Joost Verhaagen & Victoria Moreno-Manzano & Elizabeth J. Br, 2022. "Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30467-5
    DOI: 10.1038/s41467-022-30467-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30467-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-30467-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Min Shang & Federica Cappellesso & Ricardo Amorim & Jens Serneels & Federico Virga & Guy Eelen & Stefania Carobbio & Melvin Y. Rincon & Pierre Maechler & Katrien Bock & Ping-Chih Ho & Marco Sandri & B, 2020. "Macrophage-derived glutamine boosts satellite cells and muscle regeneration," Nature, Nature, vol. 587(7835), pages 626-631, November.
    2. Bradley T. Lang & Jared M. Cregg & Marc A. DePaul & Amanda P. Tran & Kui Xu & Scott M. Dyck & Kathryn M. Madalena & Benjamin P. Brown & Yi-Lan Weng & Shuxin Li & Soheila Karimi-Abdolrezaee & Sarah A. , 2015. "Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury," Nature, Nature, vol. 518(7539), pages 404-408, February.
    3. Di Wu & Ying Jin & Tatiana M. Shapiro & Abhishek Hinduja & Peter W. Baas & Veronica J. Tom, 2020. "Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    4. Victor Bellver-Landete & Floriane Bretheau & Benoit Mailhot & Nicolas Vallières & Martine Lessard & Marie-Eve Janelle & Nathalie Vernoux & Marie-Ève Tremblay & Tobias Fuehrmann & Molly S. Shoichet & S, 2019. "Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    5. Charles N. Serhan, 2014. "Pro-resolving lipid mediators are leads for resolution physiology," Nature, Nature, vol. 510(7503), pages 92-101, June.
    6. Paul T E Cusack, 2020. "The Human Brain," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 31(3), pages 24261-24266, October.
    7. Philippa M. Warren & Stephanie C. Steiger & Thomas E. Dick & Peter M. MacFarlane & Warren J. Alilain & Jerry Silver, 2018. "Rapid and robust restoration of breathing long after spinal cord injury," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    8. Elizabeth J. Bradbury & Lawrence D. F. Moon & Reena J. Popat & Von R. King & Gavin S. Bennett & Preena N. Patel & James W. Fawcett & Stephen B. McMahon, 2002. "Chondroitinase ABC promotes functional recovery after spinal cord injury," Nature, Nature, vol. 416(6881), pages 636-640, April.
    9. Yi Li & Xuelian He & Riki Kawaguchi & Yu Zhang & Qing Wang & Aboozar Monavarfeshani & Zhiyun Yang & Bo Chen & Zhongju Shi & Huyan Meng & Songlin Zhou & Junjie Zhu & Anne Jacobi & Vivek Swarup & Philli, 2020. "Microglia-organized scar-free spinal cord repair in neonatal mice," Nature, Nature, vol. 587(7835), pages 613-618, November.
    10. Warren J. Alilain & Kevin P. Horn & Hongmei Hu & Thomas E. Dick & Jerry Silver, 2011. "Functional regeneration of respiratory pathways after spinal cord injury," Nature, Nature, vol. 475(7355), pages 196-200, July.
    11. Elizabeth J. Bradbury & Emily R. Burnside, 2019. "Moving beyond the glial scar for spinal cord repair," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Julia Kolb & Vasiliki Tsata & Nora John & Kyoohyun Kim & Conrad Möckel & Gonzalo Rosso & Veronika Kurbel & Asha Parmar & Gargi Sharma & Kristina Karandasheva & Shada Abuhattum & Olga Lyraki & Timon Be, 2023. "Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Wanjie Wu & Yingzhu He & Yujun Chen & Yiming Fu & Sicong He & Kai Liu & Jianan Y. Qu, 2024. "In vivo imaging in mouse spinal cord reveals that microglia prevent degeneration of injured axons," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Myungsik Yoo & Muntasir Khaled & Kurt M Gibbs & Jonghun Kim & Björn Kowalewski & Thomas Dierks & Melitta Schachner, 2013. "Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-12, March.
    5. Floriane Bretheau & Adrian Castellanos-Molina & Dominic Bélanger & Maxime Kusik & Benoit Mailhot & Ana Boisvert & Nicolas Vallières & Martine Lessard & Matthias Gunzer & Xiaoyu Liu & Éric Boilard & Ni, 2022. "The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    6. Yongheng Fan & Xianming Wu & Sufang Han & Qi Zhang & Zheng Sun & Bing Chen & Xiaoyu Xue & Haipeng Zhang & Zhenni Chen & Man Yin & Zhifeng Xiao & Yannan Zhao & Jianwu Dai, 2023. "Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Abigail B. Schneider & Bridget Leonard, 2022. "From anxiety to control: Mask‐wearing, perceived marketplace influence, and emotional well‐being during the COVID‐19 pandemic," Journal of Consumer Affairs, Wiley Blackwell, vol. 56(1), pages 97-119, March.
    8. Odelaisy León-Triana & Julián Pérez-Beteta & David Albillo & Ana Ortiz de Mendivil & Luis Pérez-Romasanta & Elisabet González-Del Portillo & Manuel Llorente & Natalia Carballo & Estanislao Arana & Víc, 2021. "Brain Metastasis Response to Stereotactic Radio Surgery: A Mathematical Approach," Mathematics, MDPI, vol. 9(7), pages 1-19, March.
    9. Mirren Charnley & Saba Islam & Guneet K. Bindra & Jeremy Engwirda & Julian Ratcliffe & Jiangtao Zhou & Raffaele Mezzenga & Mark D. Hulett & Kyunghoon Han & Joshua T. Berryman & Nicholas P. Reynolds, 2022. "Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Hamed Nili & Alexander Walther & Arjen Alink & Nikolaus Kriegeskorte, 2020. "Inferring exemplar discriminability in brain representations," PLOS ONE, Public Library of Science, vol. 15(6), pages 1-28, June.
    11. Linzmajer, Marc & Hubert, Mirja & Hubert, Marco, 2021. "It’s about the process, not the result: An fMRI approach to explore the encoding of explicit and implicit price information," Journal of Economic Psychology, Elsevier, vol. 86(C).
    12. Natalie J Shook & Barış Sevi & Jerin Lee & Benjamin Oosterhoff & Holly N Fitzgerald, 2020. "Disease avoidance in the time of COVID-19: The behavioral immune system is associated with concern and preventative health behaviors," PLOS ONE, Public Library of Science, vol. 15(8), pages 1-15, August.
    13. Cristina Lázaro-Pérez & José Ángel Martínez-López & José Gómez-Galán, 2020. "Addictions in Spanish College Students in Confinement Times: Preventive and Social Perspective," Social Sciences, MDPI, vol. 9(11), pages 1-21, October.
    14. Yashika Arora & Pushpinder Walia & Mitsuhiro Hayashibe & Makii Muthalib & Shubhajit Roy Chowdhury & Stephane Perrey & Anirban Dutta, 2021. "Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans," PLOS Computational Biology, Public Library of Science, vol. 17(10), pages 1-38, October.
    15. Elvisa Drishti & Bresena Kopliku & Drini Imami, 2022. "Active political engagement, political patronage and local labour markets – The example of Shkoder," International Journal of Manpower, Emerald Group Publishing Limited, vol. 44(6), pages 1118-1142, April.
    16. Nguyen, Ha Trong & Brinkman, Sally & Le, Huong Thu & Zubrick, Stephen R. & Mitrou, Francis, 2022. "Gender differences in time allocation contribute to differences in developmental outcomes in children and adolescents," Economics of Education Review, Elsevier, vol. 89(C).
    17. Gricelda Herrera-Franco & Néstor Montalván-Burbano & Carlos Mora-Frank & Lady Bravo-Montero, 2021. "Scientific Research in Ecuador: A Bibliometric Analysis," Publications, MDPI, vol. 9(4), pages 1-34, December.
    18. Sofie L. Valk & Ting Xu & Casey Paquola & Bo-yong Park & Richard A. I. Bethlehem & Reinder Vos de Wael & Jessica Royer & Shahrzad Kharabian Masouleh & Şeyma Bayrak & Peter Kochunov & B. T. Thomas Yeo , 2022. "Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    19. Rosen Valchev & Cosmin Ilut, 2017. "Economic Agents as Imperfect Problem Solvers," 2017 Meeting Papers 1285, Society for Economic Dynamics.
    20. Florent Meyniel, 2020. "Brain dynamics for confidence-weighted learning," PLOS Computational Biology, Public Library of Science, vol. 16(6), pages 1-27, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30467-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.