Neuroinflammation at single cell level: What is new?

Author(s)

Brandao, W. N. ^[1] ; De Oliveira, M. G. ^[1] ; Andreoni, R. T. ^[1] ; Nakaya, H. ^[2] ; Farias, A. S. ^{[3, 4]} ; Peron, J. P. S. ^{[5, 1, 6]}

Affiliation

^[1] Univ Sao Paulo, Neuroimmune Interact Lab, Dept Immunol, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Autoimmune Res Lab, Dept Genet Microbiol & Immunol, Campinas - Brazil

^[4] Expt Med Res Cluster EMRC, Div Immune Mediated Dis, Campinas - Brazil

^[5] Univ Sao Paulo, Sci Platform Pasteur, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Immunopathol & Allergy Post Grad Program, Sch Med, Sao Paulo - Brazil

• Document type: Review article
• Source: Journal of Leukocyte Biology; AUG 2020.
• Web of Science Citations: 0

Abstract

Multiple sclerosis is a chronic and demyelinating disease of the central nervous system (CNS), most prevalent in women, and with an important social and economic cost worldwide. It is triggered by self-reacting lymphocytes that infiltrate the CNS and initiate neuroinflammation. Further, axonal loss and neuronal death takes place, leading to neurodegeneration and brain atrophy. The murine model for studying MS, experimental autoimmune encephalomyelitis (EAE), consists in immunizing mice with myelin-derived epitopes. APCs activate encephalitogenic T CD4 and CD8 lymphocytes that migrate mainly to the spinal cord resulting in neuroinflammation. Most of the knowledge on the pathophysiology and treatment of MS was obtained from EAE experiments, as Th17 cells, anti-alpha4 blocking Abs and the role of microbiota. Conversely, recent technology breakthroughs, such as CyTOF and single-cell RNA-seq, promise to revolutionize our understanding on the mechanisms involved both in MS and EAE. In fact, the importance of specific cellular populations and key molecules in MS/EAE is a constant matter of debate. It is well accepted that both Th1 and Th17 T CD4 lymphocytes play a relevant role in disease initiation after re-activation in situ. What is still under constant investigation, however, is the plasticity of the lymphocyte population, and the individual contribution of both resident and inflammatory cells for the progression or recovery of the disease. Thus, in this review, new findings obtained after single-cell analysis of blood and central nervous system infiltrating cells from MS/EAE and how they have contributed to a better knowledge on the cellular and molecular mechanisms of neuroinflammation are discussed. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/21934-5 - Network statistics: theory, methods, and applications
• Grantee: André Fujita
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 17/50137-3 - Long noncoding RNA interplay with the host microbiome may determine mucosal influenza vaccine immunogenicity
• Grantee: Helder Takashi Imoto Nakaya
• Support type: Regular Research Grants
• FAPESP's process: 17/26170-0 - Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination
• Grantee: Jean Pierre Schatzmann Peron
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 12/19278-6 - Systems biology of long non-coding RNAs
• Grantee: Helder Takashi Imoto Nakaya
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 17/22504-1 - TAM receptors and their ligands Gas6 and Pros1 on the ZIKV Congenital Syndrome in Experimental Models
• Grantee: Jean Pierre Schatzmann Peron
• Support type: Regular Research Grants
• FAPESP's process: 17/21363-5 - Regulation of JAK/STAT/SOCS in the ontogen of IFNg-producing cells derivated from encephalitogenic Th17 cells during the clinical evolution of experimental autoimmune encephalomyelitis
• Grantee: Alessandro dos Santos Farias
• Support type: Regular Research Grants
• FAPESP's process: 18/14933-2 - Integrative biology applied to human health
• Grantee: Helder Takashi Imoto Nakaya
• Support type: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 19/06372-3 - Multiparametric flow cytometry
• Grantee: Alessandro dos Santos Farias
• Support type: Multi-user Equipment Program