Antoine Louveau Laboratory

Research

In the Louveau lab, we study the role of the surrounding of the brain and spinal cord, called the meninges, in normal and pathological brain function. Contrary to the parenchyma that is virtually devoid of immune cells, except microglia, under normal conditions, the meninges harbor a rich and dynamic immune environment. The meninges are strategically positioned to be the interface between the periphery and the parenchyma, but we still do not fully understand how the meningeal compartment is interfering with brain function.

We previously showed that the meninges contain a network of lymphatic vessels that ensures the drainage of central nervous system constituents and immune cells and found that their disruption affects the development of neurological disorders like multiple sclerosis and Alzheimer’s disease. However, we still don’t understand how the meningeal lymphatic vessels impact the meningeal and brain compartments under normal and pathological conditions.

We observed large remodeling of the meningeal immune compartment and meningeal lymphatic during critical windows of normal brain development, but also under numerous neurological conditions. We therefore aim to understand how the meningeal lymphatic vasculature and immune compartment impact the brain under normal and pathological conditions. By studying the role of the meninges in brain function, our ultimate goal is to identify therapeutic approaches for neurological disorders that target the meningeal compartment.

Selected Publications

Tavares GA, Louveau A. (2021) Meningeal Lymphatics: An Immune Gateway for the Central Nervous System. Cells 10(12):3385. PMID: 34943894; PMCID: PMC8699870

Da Mesquita S, Papadopoulos Z, Dykstra T, Brase L, Farias FG, Wall M, Jiang H, Kodira CD, de Lima KA, Herz J, Louveau A, Goldman DH, Salvador AF, Onengut-Gumuscu S, Farber E, Dabhi N, Kennedy T, Milam MG, Baker W, Smirnov I, Rich SS; Dominantly Inherited Alzheimer Network, Benitez BA, Karch CM, Perrin RJ, Farlow M, Chhatwal JP, Holtzman DM, Cruchaga C, Harari O, Kipnis J. (2021) Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy. Nature 593(7858):255-260. PMID: 33911285; PMCID: PMC8817786

Frederick N, Louveau A. (2020) Meningeal lymphatics, immunity and neuroinflammation. Curr Opin Neurobiol. 62:41-47. PMID: 31816570

Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. (2018) CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 21(10):1380-1391. PMID: 30224810

Da Mesquita S*, Louveau A*, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, Contarino C, Onengut-Gumuscu S, Farber E, Raper D, Viar KE, Powell RD, Baker W, Dabhi N, Bai R, Cao R, Hu S, Rich SS, Munson JM, Lopes MB, Overall CC, Acton ST, Kipnis J. (2018) Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease. Nature 560(7717):185-191. PMID: 30046111

Cronk JC*, Filiano AJ*, Louveau A, Marin I, Marsh R, Ji E, Goldman DH, Smirnov I, Geraci N, Acton S, Overall CC, Kipnis J (2018)  Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia. J Exp Med. 215(6):1627-1647. PMID: 29643186; PMCID: PMC5987928

Louveau A, Filiano AJ, Kipnis J. (2018) Meningeal whole mount preparation and characterization of neural cells by flow cytometry. Curr Protoc Immunol. 121(1). PMID: 30008983

Louveau A. (2018) Meningeal Immunity, Drainage, and Tertiary Lymphoid Structure Formation. Methods Mol Biol. 1845:31-45. PMID: 30141006

Herz J, Louveau A, Da Mesquita S, Kipnis J. (2018) Morphological and Functional Analysis of CNS-Associated Lymphatics. Methods Mol Biol. 1846:141-151. PMID: 30242757

Louveau A, Kipnis J. (2018) Sex, Gut, and Microglia. Dev Cell 44(2):137-138. PMID: 29401417

Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. (2017) Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife 2017 Oct 3;6. PMID: 28971799; PMCID: PMC5626482

Louveau A*, Plog BA*, Antila S*, Alitalo K, Nedergaard M, Kipnis J. (2017) Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J Clin Invest. 127(9):3210-3219. PMID: 28862640; PMCID: PMC5669566

Jung E, Gardner D, Choi D, Park E, Jin Seong Y, Yang S, Castorena-Gonzalez J, Louveau A, Zhou Z, Lee GK, Perrault DP, Lee S, Johnson M, Daghlian G, Lee M, Jin Hong Y, Kato Y, Kipnis J, Davis MJ, Wong AK, Hong YK. (2017) Development and Characterization of A Novel Prox1-EGFP Lymphatic and Schlemm's Canal Reporter Rat. Sci Rep. 7(1):5577. PMID: 28717161; PMCID: PMC5514086

Cronk JC, Herz J, Kim TS, Louveau A, Moser EK, Sharma AK, Smirnov I, Tung KS, Braciale TJ, Kipnis J. (2017) Influenza A induces dysfunctional immunity and death in MeCP2-overexpressing mice. JCI Insight 2(2):e88257. PMID: 28138553; PMCID: PMC5256138

Cisternas P, Louveau A, Bueno SM, Kalergis AM, Boudin H, Riedel CA. (2016) Gestational Hypothyroxinemia Affects Glutamatergic Synaptic Protein Distribution and Neuronal Plasticity Through Neuron-Astrocyte Interplay. Mol Neurobiol. 53(10):7158-7169. PMID: 26687181

Louveau A*, Da Mesquita S*, Kipnis J. (2016) Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of Multiple Sclerosis and Alzheimer's Disease? Neuron 91(5):957-973. PMID: 27608759; PMCID: PMC5019121

Raper D*, Louveau A*, Kipnis J. (2016) How Do Meningeal Lymphatic Vessels Drain the CNS? Trends Neurosci. 39(9):581-586. PMID: 27460561; PMCID: PMC5002390

Louveau A, Nerrière-Daguin V, Vanhove B, Naveilhan P, Neunlist M, Nicot A, Boudin H. (2015) Targeting the CD80/CD86 costimulatory pathway with CTLA4-Ig directs microglia toward a repair phenotype and promotes axonal outgrowth. Glia 63(12):2298-312. PMID: 26212105

Louveau A. (2015) Cerebral lymphatic drainage: implication in the brain immune privilege. Med Sci (Paris) 31(11):953-6. PMID: 26576598

Louveau A, Harris TH, Kipnis J. (2015) Revisiting Revisiting the Mechanisms of CNS Immune Privilege. Trends Immunol. 36(10):569-577. PMID: 26431936; PMCID: PMC4593064

Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337-41. PMID: 26030524; PMCID: PMC4506234

Louveau A, Angibaud J, Haspot F, Opazo MC, Thinard R, Thepenier V, Baudouin SJ, Lescaudron L, Hulin P, Riedel CA, Boudin H. (2013) Impaired spatial memory in mice lacking CD3ζ is associated with altered NMDA and AMPA receptors signaling independent of T-cell deficiency. J Neurosci. 33(47):18672-85. PMID: 24259588

Angibaud J, Baudouin SJ, Louveau A, Nerrière-Daguin V, Bonnamain V, Csaba Z, Dournaud P, Naveilhan P, Noraz N, Pellier-Monnin V, Boudin H. (2012) Ectopic expression of the immune adaptor protein CD3zeta in neural stem/progenitor cells disrupts cell-fate specification. J Mol Neurosci. 46(2):431-41. PMID: 21809042

Angibaud J*, Louveau A*, Baudouin SJ, Nerrière-Daguin V, Evain S, Bonnamain V, Hulin P, Csaba Z, Dournaud P, Thinard R, Naveilhan P, Noraz N, Pellier-Monnin V, Boudin H. (2011) The immune molecule CD3zeta and its downstream effectors ZAP-70/Syk mediate ephrin signaling in neurons to regulate early neuritogenesis. J Neurochem. 119(4):708-22. PMID: 21895656