ISN Satellite Meeting on IMMUNE CELLS AND THE CNS

A FOCUS BY THE

Organizers: Violetta Zujovic and Séverine Boillée

Venue: Campus de Cély, Cély, France (suburb of Paris)

 Sponsors: ENP, ISN, ARSEP, Neuratris

Our program gathered the top specialists of the field of immune cell roles in the CNS. International researcher shared their point of view on different technological approaches and different topics: development, autoimmune or neurodegenerative diseases with a common interest in neuroimmunology. 

The concept of gathering not only during scientific session but also during the breaks/evenings enabled fruitful discussions and opened the way to future collaborations. Likewise the proximity with experienced researchers, gave to the students and the post-doctoral fellows the opportunity to exchange on their scientific concerns but also collect advice for their career evolution.

The scientific program was divided in 5 symposia dealing with the implication of immune cells in health and diseases or after injury. In detail:

With symposium 1 “unraveling immune cell implication in neurological diseases”, we got introduced to several transcriptomic data available from cohorts of human aging populations (P. De Jager). Several modules, enriched in microglia or age regulated could be extracted from these results and are important for the community to relate to their own research. The next presentation focused on different pathways implicated in Parkinson’s disease (PD) with a focus on genetic causes (O. Corti). Interestingly, different genes implicated in dopaminergic neuron degeneration are also important players in the inflammatory process taking place in PD. More specifically the work highlighted the links between Pink, Parkin and the inflammasome from studies obtained in mouse microglial cells and monocytes derived from patients. On the other side of the spectrum, the implication of environmental risk factors was presented for Multiple Sclerosis (MS) patients (I. Kockum). The most significant factor was smoking which increases the risk of MS and correlates with the amount of smoking but is apparently not linked to nicotine.

 Symposium 2 “microglial cell activation states” highlighted a new pathway in Alzheimer’s disease linked to the inflammasome, which involves ASC speckles and links it to the plaques present in AD affected brains (M. Heneka). A second aspect described microglial cells implication in the context of cognitive deficits linked to premature birth (P. Gressens). Microglial cells showed a delayed pro-repair phenotype and several candidates implicated in microglial-synaptic communication where highlighted. Another emphasize on the interactions between microglial cells and neural synapses was shown in several models of different neuronal affections or aging (M-E Tremblay). More specifically detailed electron microscopic histology described the discovery of intriguing dark microglial cells, which functions are unknown and opens up an entire field of research. 

 Symposium 3 “from injury to repair, role of immune cells”. In this symposium we had an overview on how innate but also adaptive immune cells can participate to degeneration but also orchestrate the repair process. Jonathan Kipnis questioned whether microglial cells are replaceable and evidenced that in a model where microglial cells were chronically depleted and replaced by engrafted macrophages, the engrafting cells do not impact healthy brain function but respond abnormally to challenges. Stefan Bittner presented the latest technique for two-photon imaging of the cervical spinal cord, which enables to follow the interaction of T cells with the microvasculature during the development of experimental autoimmune encephalomyelitis. He notably depicted the different steps leading to T cells invasion of the CNS. Jeffrey Huang described that the molecule IL4I1 is expressed by alternatively activated microglia/macrophages and that IL4I1 deficient mice display enhanced inflammation, impaired remyelination and increased axonal injury. Moreover, IL4I1 gain-of-function significantly reduced inflammation in lesions resulting in increased remyelination. 

Symposium 4 “when immunity takes part in neurodegeneration” highlighted the implication of specific pathways in models of neurodegenerative diseases. More specifically, the role of the purinergic receptor P2X7 was studied in detailed in AD models (C. Delarasse). P2X7 deficiency improved memory in AD mice and an in depth study of the different potential immune cell players concluded to the implication of T cells and specific chemokines. The second aspect focused on the implication of major histocompatibility comples (MHC) in Amyotrophic Lateral Sclerosis (ALS) models (C. Bendotti). MHC was implicated in disease progression and acted on axon regeneration implicating different cell types.

 Symposium 5 “challenges of human microglial cells” was focused on different protocols to obtain microglial cells or macrophages from humans to study their transcriptome or their functional defects during aging or in different neurological diseases. The first speaker (P. Mesci) described protocols to derive macrophages from iPSc and applied them to study consequences of infections by Zika virus and showed that the virus could be transmitted to neuronal precursor cells by macrophages. Another highlight was on Rett syndrome showing the effect of the mutation on different macrophage functions. Protocols to obtain microglial cells from iPSc were described in detail (J. Muffat) showing that it was possible to obtain mature ramified microglial cells in culture to study their cytokine and transcriptome profiles and that developing 3D cultures will help study neuron-microglia interactions. Finally, the transcriptome of microglial cells was performed from human post-mortem brains (B. Eggen). Different analyses were performed to compare the profile for example during aging or between mice and humans. This set of data is of high interest for the community and future approaches will study more in detail inflammation challenges on chromatin defects. 

 In conclusion this was a really successful meeting with an overview of the different aspects of immune cell implication in the nervous system. Each presentation led to intense discussion after each talk and during breaks, many interactions and brainstorming on how our collective effort will impact the field of neuroimmunology. We got asked by many of the participants whether we planned to make this a yearly meeting so we would encourage scientists to organize the follow up satellite meeting on immune cells and the CNS at the next ISN meeting.