The Antibody Dependant Neurite Outgrowth Modulation Response (ADNM) involvement in Spinal Cord Injury

Abstract Spinal Cord Injury (SCI) represents a major medical challenge. At present, there is still no cure to treat it efficiently and enable functional recovery at the level of cavity. Previously, we demonstrated that inflammation determine the fate of the physiopathology. In an attempt to decipher the molecular mechanisms involved in this process, we performed a meta-analysis of our spatio-temporal proteomic studies in time course of SCI. This highlighted the presence of IgG isotypes in both the tissues and secretome of spinal cord explants. These IgGs which were detected even if no SCI occurs in spinal cord, followed the time course and the spatial repartition with presence of IgG1 and IgG2 subclasses (a, b, c). IgG1 was clearly mostly abundant at 12h and switch in time course to IgG2a at 24h then stay predominant 3, 7 and 10 days after SCI. A protein related to IgM as well as a variable heavy chain were detected only 12h after lesion. Interestingly, RhoA inhibitor treatment influences the IgG isotypes switching preferentially to IgG2c. By transcriptomic analyses using 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 dopaminergic neurons N27 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 regulate neurites outgrowth. Therefore, we propose a new view of the spinal cord injury response involving an antibody dependent neurite outgrowth modulation (ADNM) which could be precursor of the neuroinflammatory response in pathological conditions.