Biology subjects

Montilla, A.

Publications and source records attributed to Montilla, A..

3 recordsLinked to original sources

bioRxiv2023

IRF5 regulates microglial myelin clearance and cholesterol metabolism after demyelination

Interferon regulatory factor 5 (IRF5), a transcription factor highly involved in innate immunity that drives microglia/macrophage towards a pro-inflammatory state, has been associated to multiple sclerosis susceptibility but its role in MS pathogenesis is unknown. Here we analysed the role of IRF5 in multiple sclerosis animal models. Irf5-/- mice showed exacerbated damage in the chronic phase of experimental autoimmune encephalomyelitis (EAE) mice, despite an initial delay in its onset, as well as after lysolecithin injection into the spinal cord. Transcriptomic and lipidomic analysis evidence a role of this transcription factor in myelin metabolism and cholesterol homeostasis. Indeed, Irf5-/- mice showed an aberrant accumulation of myelin debris and lipidic structures, such as CE-containing lipid droplets and cholesterol crystals, suggesting that myelin-derived lipids are not properly processed. Cholesterol crystal accumulation leads to an aberrant inflammatory response, which block oligodendrocyte migration into the core of demyelinated lesion and remyelination. Pharmacologically facilitating cholesterol transport reduces lipid droplet accumulation and ameliorates EAE exacerbated damage in Irf5-/- mice. These results reveal for the first time the role of Irf5, a transcription factor necessary to orchestrate the immune responses, in phagocytes lipid metabolism which could be pivotal in regenerative responses such as remyelination.

neuroscience↗

bioRxiv2022

Microglia and meningeal macrophages depletion delay the onset of experimental autoimmune encephalomyelitis

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population and Ccr2RFP/+fmsEGFP/+ mice, to distinguish peripheral macrophages and microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2+ macrophages into demyelinating lesions and spinal cord parenchyma. PLX5622 treatment did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of CD80 co-stimulatory molecule in dendritic and myeloid cells and reduced T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data points to a specific role of CNS microglia meningeal macrophages in antigen presentation and T cell reactivation at initial stages of the EAE model.

neuroscience↗

bioRxiv2018

Evolution of international collaborative research efforts to develop non-Cochrane systematic reviews

This research-on-research study describes effortsto develop non-Cochrane systematic reviews (SRs) by analysing demographical and time-course collaborations between international institutions using protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO) or published in scientific journals. We have published an a priori protocol to develop this study. Protocols published in scientific journals were searched in MEDLINE/PubMed and Embase databases using the query terms systematic review[Title] AND protocol[Title] from February 2011 to December 2017. Protocols registered at PROSPERO during the same period were obtained by web scraping all non-Cochrane records with a Python script. After excluding protocols with less than 90% fulfilled or duplicated, they were classified as published only in PROSPERO, only in journals, or in both journals and PROSPERO. Results of data and metadata extraction using text-mining processes were curated by two reviewers. Datasets and R scripts are freely available to facilitate reproducibility. We obtained 20,814 protocols of non-Cochrane SRs. While unique protocols by re-viewers institutions from 60 countries were the most frequent, to prepare collaborative protocols a median of 6 (2-150) institutions were involved from 130 different countries. Ranked list of countries involved in overall protocol production were the UK, the U.S., Australia, Brazil, China, Canada, the Netherlands, Germany, and Italy. Most protocols were registered only in PROSPERO. However, the number of protocols published in scientific journals (924) or in both PROSPERO and journals (807) has progressively increased over the last three years. Syst Rev and BMJ Open published more than half of the total protocols. While most productive countries were involved in unique and collaborative protocols, less productive countries only participated in collaborative protocols that were mainly published only in PROSPERO. Our results suggest that although most countries were involved in producing in solitary protocols of non-Cochrane SRs during the study period, it would be desirable to develop new strategies to promote international collaborations, especially with less productive countries.

scientific communication and education↗