Differential Roles of TREM2+ Microglia in Anterograde and Retrograde Axonal Injury Models
Manich, Gemma (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Gómez-López, Ariadna Regina (Universitat Autònoma de Barcelona. Institut de Neurociències)
Almolda Ardid, Beatriz (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Villacampa, Nàdia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Recasens, Mireia (Universitat Autònoma de Barcelona. Institut de Neurociències)
Shrivastava, Kalpana (Universitat Autònoma de Barcelona. Institut de Neurociències)
González, Berta (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Castellano López, Bernardo (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Data:	2020
Resum:	Microglia are the main immune cells of the central nervous system (CNS), and they are devoted to the active surveillance of the CNS during homeostasis and disease. In the last years, the microglial receptor Triggering Receptor Expressed on Myeloid cells-2 (TREM2) has been defined to mediate several microglial functions, including phagocytosis, survival, proliferation, and migration, and to be a key regulator of a new common microglial signature induced under neurodegenerative conditions and aging, also known as disease-associated microglia (DAM). Although microglial TREM2 has been mainly studied in chronic neurodegenerative diseases, few studies address its regulation and functions in acute inflammatory injuries. In this context, the present work aims to study the regulation of TREM2 and its functions after reparative axonal injuries, using two-well established animal models of anterograde and retrograde neuronal degeneration: the perforant pathway transection (PPT) and the facial nerve axotomy (FNA). Our results indicate the appearance of a subpopulation of microglia expressing TREM2 after both anterograde and retrograde axonal injury. TREM2+ microglia were not directly related to proliferation, instead, they were associated with specific recognition and/or phagocytosis of myelin and degenerating neurons, as assessed by immunohistochemistry and flow cytometry. Characterization of TREM2+ microglia showed expression of CD16/32, CD68, and occasional Galectin-3. However, specific singularities within each model were observed in P2RY12 expression, which was only downregulated after PPT, and in ApoE, where de novo expression was detected only in TREM2+ microglia after FNA. Finally, we report that the pro-inflammatory or anti-inflammatory cytokine microenvironment, which may affect phagocytosis, did not directly modify the induction of TREM2+ subpopulation in any injury model, although it changed TREM2 levels due to modification of the microglial activation pattern. In conclusion, we describe a unique TREM2+ microglial subpopulation induced after axonal injury, which is directly associated with phagocytosis of specific cell remnants and show different phenotypes, depending on the microglial activation status and the degree of tissue injury.
Ajuts:	Ministerio de Economía y Competitividad BFU2014-55459 Agencia Estatal de Investigación BFU2017-87843-R
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	IL-10 (interleukin-10) ; IL-6 (interleukin-6) ; Phagocytosis ; Proliferation ; Neuroinflammation ; Microglial clusters ; P2RY12 ; APOE
Publicat a:	Frontiers in cellular neuroscience, Vol. 14 (november 2020) , ISSN 1662-5102

DOI: 10.3389/fncel.2020.567404
PMID: 33328887

25 p, 17.1 MB

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