Unique expression pattern of circulating exosomal miRNA correlates with CNS pathology
Abstract
Background and objectives: To investigate the total circulating exosome transcriptome in animal models of two different CNS pathologic conditions, autoimmune demyelination and traumatic brain injury (TBI). Methods: Next generation sequencing (NGS) was used to define the global RNA profile of blood exosomes in the MOG-induced EAE model of autoimmune demyelination and TBI mice model. We analyzed 5 million reads per sample, including a detailed analysis of microRNAs (miRNAs) differentially expressed in EAE versus control mice and versus TBI model. Results: Exosomal RNA NGS revealed 10 different classes of transcripts including miRNA. MiRNA numbers from EAE and TBI mice showed trend to be lower versus control mice. The differentially expressed miRNAs were found in all three sequential EAE time points: early stage post mice immunization (EAEp), peak of disease (EAEa) and recovery (EAEl). The differential expression pattern of miRNA in EAE versus TBI correlated with their involvement in activation or inhibition of immune response. In the early stage of EAE miRNA-335-5p and miRNA-411-5p were upregulated versus TBI. At the peak of disease six miRNAs were most upregulated, miRNA-27a-3p, miRNA-141-3p, miRNA27b-3p, miRNA-195a-5p, miRNA21a-5p and miRNA-99a-5p. The six most upregulated miRNA at the recovery time point of EAE, miRNA-27b-3p, miRNA 141-3p, miRNA 27a-3p, miRNA-127-3p, miRNA-429-3p and let-7b-5p were associated with inhibition of immune response and enhancement of immunoregulation. Interestingly, it was found that similar pattern of downregulated miRNAs versus TBI were present at all three of EAE time points. Bioinformatic analysis of protein genes targeted by the most differentially expressed miRNAs revealed a numbers of proteins involved in neuroinflammation both in EAE and TBI models. In the early phase of EAE, three protein transcripts, Hdac9, Syt7 and NT5c2 serve as an epigenetic switch controlling T cell fate and cytokine production. In recovery of EAE RoRb, a member of ROR nuclear receptor family involved in Th17 cell differentiation was inhibited. Discussion: These data indicate that different type of CNS pathology, autoimmune demyelination versus TBI is associated with different pattern of miRNA expression in circulating exosomes which may suggest their differential role in these two CNS pathologies.
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BibTeX
@article{selmaj2026unique,
title = {{Unique expression pattern of circulating exosomal miRNA correlates with CNS pathology}},
author = {Krzysztof Selmaj and Magda Tinsley and Jerome Badaut and Marcin P Mycko},
journal = {Frontiers in Immunology},
year = {2026},
month = jul,
doi = {10.3389/fimmu.2026.1848236},
url = {https://hal.science/hal-05788113v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Unique expression pattern of circulating exosomal miRNA correlates with CNS pathology
AU - Krzysztof Selmaj
AU - Magda Tinsley
AU - Jerome Badaut
AU - Marcin P Mycko
PY - 2026
DA - 2026/07/09
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1848236
UR - https://hal.science/hal-05788113v1
AB - Background and objectives: To investigate the total circulating exosome transcriptome in animal models of two different CNS pathologic conditions, autoimmune demyelination and traumatic brain injury (TBI). Methods: Next generation sequencing (NGS) was used to define the global RNA profile of blood exosomes in the MOG-induced EAE model of autoimmune demyelination and TBI mice model. We analyzed 5 million reads per sample, including a detailed analysis of microRNAs (miRNAs) differentially expressed in EAE versus control mice and versus TBI model. Results: Exosomal RNA NGS revealed 10 different classes of transcripts including miRNA. MiRNA numbers from EAE and TBI mice showed trend to be lower versus control mice. The differentially expressed miRNAs were found in all three sequential EAE time points: early stage post mice immunization (EAEp), peak of disease (EAEa) and recovery (EAEl). The differential expression pattern of miRNA in EAE versus TBI correlated with their involvement in activation or inhibition of immune response. In the early stage of EAE miRNA-335-5p and miRNA-411-5p were upregulated versus TBI. At the peak of disease six miRNAs were most upregulated, miRNA-27a-3p, miRNA-141-3p, miRNA27b-3p, miRNA-195a-5p, miRNA21a-5p and miRNA-99a-5p. The six most upregulated miRNA at the recovery time point of EAE, miRNA-27b-3p, miRNA 141-3p, miRNA 27a-3p, miRNA-127-3p, miRNA-429-3p and let-7b-5p were associated with inhibition of immune response and enhancement of immunoregulation. Interestingly, it was found that similar pattern of downregulated miRNAs versus TBI were present at all three of EAE time points. Bioinformatic analysis of protein genes targeted by the most differentially expressed miRNAs revealed a numbers of proteins involved in neuroinflammation both in EAE and TBI models. In the early phase of EAE, three protein transcripts, Hdac9, Syt7 and NT5c2 serve as an epigenetic switch controlling T cell fate and cytokine production. In recovery of EAE RoRb, a member of ROR nuclear receptor family involved in Th17 cell differentiation was inhibited. Discussion: These data indicate that different type of CNS pathology, autoimmune demyelination versus TBI is associated with different pattern of miRNA expression in circulating exosomes which may suggest their differential role in these two CNS pathologies.
SN - 1664-3224
SN - 1664-3224
ER -