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Combining in vivo spectral biphoton imaging and multiparametric cytometry to characterize the dynamics of the innate immune response in a multiple sclerosis mouse model

Periodic Reporting for period 1 - InnateMSDyn (Combining in vivo spectral biphoton imaging and multiparametric cytometry to characterize the dynamics of the innate immune response in a multiple sclerosis mouse model)

Periodo di rendicontazione: 2016-07-01 al 2018-06-30

Multiple sclerosis is a disease affecting more than 2.3 million people worldwide. Combining the use of “multicolor” mice and advanced imaging techniques, my aim was to characterize the dynamics and the diversity of immune cells in a mice model of multiple sclerosis as well as axonal degeneration. We correlated the data with evolution of motor deficits. We showed that innate immune cells are of first importance in the spinal cord pathogenesis, with a complex recruitment and activation pattern. Finally, we treated the mice with anti-VEGF antibody to better understand the role of VEGF in this pathology and evaluate its potential as therapeutic drugs. The treatment allowed the mice to better recover after disease peak, leading to the idea that it could be helpful to improve patients’ quality of life.
The first main results are that innate immune cells, i.e. neutrophils and monocytes, enter the spinal cord before T and B cells and are even more numerous. Monocytes mature once inside the spinal cord into monocyte-derived dendritic cells, and microglial cells are only afterwards recruited to the inflamed areas. This data highlight the important role of innate immune cells in multiple sclerosis. These results have been published in an open-access peer-reviewed scientific journal and presented in 7 national and international scientific meetings, and 7 popularized events open to public.
The second main result is the beneficial effect of anti-VEGF treatment on the mice, allowing a better recovery after disease peak. This data is not published yet because we are still working on precising the underlying mechanisms.
Knowledge about all the immune cells involved in multiple sclerosis is very important to understand and thus treat the disease. New therapeutic drugs are urgently required to help people suffering from multiple sclerosis, and we truly hope our results will be used as such. Moreover, anti-VEGF treatment is already used in other cases, thus secondary effects are quite known and therefore manageable. The potential socio-economic impact is a better quality of life for all patients suffering of multiple sclerosis.
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