Cargando…
The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury
Spinal cord injury (SCI) represents a major medical challenge. At present, there is still no cure to treat it efficiently and enable functional recovery below the injury site. Previously, we demonstrated that inflammation determines the fate of the physiopathology. To decipher the molecular mechanis...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245426/ https://www.ncbi.nlm.nih.gov/pubmed/35784350 http://dx.doi.org/10.3389/fimmu.2022.882830 |
_version_ | 1784738736816259072 |
---|---|
author | Capuz, Alice Karnoub, Mélodie-Anne Osien, Sylvain Rose, Mélanie Mériaux, Céline Fournier, Isabelle Devos, David Vanden Abeele, Fabien Rodet, Franck Cizkova, Dasa Salzet, Michel |
author_facet | Capuz, Alice Karnoub, Mélodie-Anne Osien, Sylvain Rose, Mélanie Mériaux, Céline Fournier, Isabelle Devos, David Vanden Abeele, Fabien Rodet, Franck Cizkova, Dasa Salzet, Michel |
author_sort | Capuz, Alice |
collection | PubMed |
description | Spinal cord injury (SCI) represents a major medical challenge. At present, there is still no cure to treat it efficiently and enable functional recovery below the injury site. Previously, we demonstrated that inflammation determines the fate of the physiopathology. To decipher the molecular mechanisms involved in this process, we performed a meta-analysis of our spatio-temporal proteomic studies in the time course of SCI. This highlighted the presence of IgG isotypes in both spinal cord explants and their secretomes. These IgGs were detected in the spinal cord even if no SCI occurred. However, during the time course following SCI, abundance of IgG1 and IgG2 subclasses (a, b, c) varied according to the spatial repartition. IgG1 was clearly mostly abundant at 12 h, and a switch to IgG2a was observed after 24 h. This IgG stayed predominant 3, 7, and 10 days after SCI. A protein related to IgM as well as a variable heavy chain were only detected 12 h after lesion. Interestingly, treatment with RhoA inhibitor influenced the abundance of the various IgG isotypes and a preferential switch to IgG2c was observed. By data reuse of rat dorsal root ganglion (DRG) neurons RNAseq datasets and RT-PCR experiments performed on cDNA from DRG sensory neurons ND7/23 and N27 dopaminergic neural cell lines, we confirmed expression of immunoglobulin heavy and light chains (constant and variable) encoding genes in neurons. We then identified CD16 and CD32b as their specific receptors in sensory neuron cell line ND7/23 and their activation regulated neurites outgrowth. These results suggest that during SCI, neuronal IgG isotypes are released to modulate neurites outgrowth. Therefore, we propose a new view of the SCI response involving an antibody dependent neurite outgrowth modulation (ADNM) which could be a precursor to the neuroinflammatory response in pathological conditions. |
format | Online Article Text |
id | pubmed-9245426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92454262022-07-01 The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury Capuz, Alice Karnoub, Mélodie-Anne Osien, Sylvain Rose, Mélanie Mériaux, Céline Fournier, Isabelle Devos, David Vanden Abeele, Fabien Rodet, Franck Cizkova, Dasa Salzet, Michel Front Immunol Immunology Spinal cord injury (SCI) represents a major medical challenge. At present, there is still no cure to treat it efficiently and enable functional recovery below the injury site. Previously, we demonstrated that inflammation determines the fate of the physiopathology. To decipher the molecular mechanisms involved in this process, we performed a meta-analysis of our spatio-temporal proteomic studies in the time course of SCI. This highlighted the presence of IgG isotypes in both spinal cord explants and their secretomes. These IgGs were detected in the spinal cord even if no SCI occurred. However, during the time course following SCI, abundance of IgG1 and IgG2 subclasses (a, b, c) varied according to the spatial repartition. IgG1 was clearly mostly abundant at 12 h, and a switch to IgG2a was observed after 24 h. This IgG stayed predominant 3, 7, and 10 days after SCI. A protein related to IgM as well as a variable heavy chain were only detected 12 h after lesion. Interestingly, treatment with RhoA inhibitor influenced the abundance of the various IgG isotypes and a preferential switch to IgG2c was observed. By data reuse of rat dorsal root ganglion (DRG) neurons RNAseq datasets and RT-PCR experiments performed on cDNA from DRG sensory neurons ND7/23 and N27 dopaminergic neural cell lines, we confirmed expression of immunoglobulin heavy and light chains (constant and variable) encoding genes in neurons. We then identified CD16 and CD32b as their specific receptors in sensory neuron cell line ND7/23 and their activation regulated neurites outgrowth. These results suggest that during SCI, neuronal IgG isotypes are released to modulate neurites outgrowth. Therefore, we propose a new view of the SCI response involving an antibody dependent neurite outgrowth modulation (ADNM) which could be a precursor to the neuroinflammatory response in pathological conditions. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9245426/ /pubmed/35784350 http://dx.doi.org/10.3389/fimmu.2022.882830 Text en Copyright © 2022 Capuz, Karnoub, Osien, Rose, Mériaux, Fournier, Devos, Vanden Abeele, Rodet, Cizkova and Salzet https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Capuz, Alice Karnoub, Mélodie-Anne Osien, Sylvain Rose, Mélanie Mériaux, Céline Fournier, Isabelle Devos, David Vanden Abeele, Fabien Rodet, Franck Cizkova, Dasa Salzet, Michel The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury |
title | The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury |
title_full | The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury |
title_fullStr | The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury |
title_full_unstemmed | The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury |
title_short | The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury |
title_sort | antibody dependant neurite outgrowth modulation response involvement in spinal cord injury |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245426/ https://www.ncbi.nlm.nih.gov/pubmed/35784350 http://dx.doi.org/10.3389/fimmu.2022.882830 |
work_keys_str_mv | AT capuzalice theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT karnoubmelodieanne theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT osiensylvain theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT rosemelanie theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT meriauxceline theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT fournierisabelle theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT devosdavid theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT vandenabeelefabien theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT rodetfranck theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT cizkovadasa theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT salzetmichel theantibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT capuzalice antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT karnoubmelodieanne antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT osiensylvain antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT rosemelanie antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT meriauxceline antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT fournierisabelle antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT devosdavid antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT vandenabeelefabien antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT rodetfranck antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT cizkovadasa antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury AT salzetmichel antibodydependantneuriteoutgrowthmodulationresponseinvolvementinspinalcordinjury |