Nogo-Receptor 1 Deficiency Has No Influence on Immune Cell Repertoire or Function during Experimental Autoimmune Encephalomyelitis

Abstract

The potential role of Nogo-66 Receptor 1 (NgR1) on immune cell phenotypes and their activation during neuroinflammatory diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), is unclear. To further understand the function of this receptor on haematopoietically-derived cells, phenotypic and functional analyses were performed using NgR1-deficient (ngr1-/-) animals. Flow cytometry-based phenotypic analyses performed on blood, spleen, thymus, lymph nodes, bone marrow and central nervous-system (CNS)-infiltrating blood cells revealed no immunological defects in naïve ngr1-/- animals versus wild-type littermate (WTLM) controls. EAE was induced by either recombinant myelin oligodendrocyte glycoprotein (rMOG), a model in which B cells are considered to contribute pathogenically, or by MOG35–55 peptide, a B cell-independent model. We have demonstrated that in ngr1-/- mice injected with MOG35–55, a significant reduction in the severity of EAE correlated with reduced axonal damage present in the spinal cord when compared to their WTLM controls. However, despite a reduction in axonal damage observed in the CNS of ngr1-/- mice at the chronic stage of disease, no clinical differences could be attributed to a specific genotype when rMOG was used as the encephalitogen. Following MOG35–55-induction of EAE, we could not derive any major changes to the immune cell populations analyzed between ngr1-/- and WTLM mice. Collectively, these data demonstrate that NgR1 has little if any effects on the repertoire of immune cells, their activation and trafficking to the CNS.

Nogo receptor complex expression dynamics in the inflammatory foci of central nervous system experimental autoimmune demyelination

“…In the acute phase, we showed that the majority of the NgR protein signal (70–75 %) was detected in inflammatory cells of lesioned areas, while lesser signal was acquired from axonal elements of white matter (~10–15 %). Although B and T cell populations were not examined in this study, it has been previously published that NgR deficiency does not affect the immune cell repertoire [ 16 ] nor the clinical outcome of EAE [ 17 ]. On the other hand, NgR has been strongly connected to cell adhesion [ 31 , 32 ], motility of microglia and its regulation [ 22 , 33 , 34 ].…”

“…The value of the Nogo-NgR pathway for control of axonal regeneration is verified by the development of Nogo-A and LINGO-1 monoclonal antibodies for clinical trials [ 14 , 15 ]. Despite the fact that NgR is key to the pathway activation, only few studies analyzing knockout mice in experimental autoimmune encephalomyelitis (EAE) [ 16 , 17 ] and few small interference RNA (siRNA) experiments have been carried out in demyelination of optic nerve tracts [ 18 , 19 ], rendering its precise function still enigmatic. In vitro experiments by Takahashi and colleagues [ 20 ] and later further progressed by David and colleagues [ 21 , 22 ] suggest that the presence of NgR in macrophages—apart from neurons or glia—could support the clearance of debris and could confine the injury away from the normal-appearing white matter tissue.…”

Μελέτη έκφρασης του Nogo-A και του υποδοχέα του στην πειραματική αυτοάνοση εγκεφαλομυελίτιδα

“…φιθςκα ιε ηα ιέπνζ ηχνα αζαθζμβναθζηά δεδμιέκα, μζ απυρεζξ πμο ηαηαηίεεκηαζ ζπεηζηά ιε ημκ νυθμ ημο Nogo-A ζηδκ ΠΑΔ είκαζ ακηζηνμουιεκεξ. Τπάνπμοκ ιεθέηεξ πμο οπμζηδνίγμοκ υηζ ημ ζοβηεηνζιέκμ ιυνζμ δε ζοιιεηέπεζ ζηδκ παεμθοζζμθμβία ηδξ ΠΑΔ [151][152] ηαζ άθθεξ πμο οπμζηδνίγμοκ ηδκ ζοιιεημπή ημο πςνίξ υιςξ κα πνμζδζμνίγμοκ ημκ νυθμ ημο (αηυια ηαζ υηακ δδιμζζεφμκηαζ ηδκ ίδζα πνμκζηή ζηζβιή ηαζ ζημ ίδζμ πενζμδζηυ) [153][154][155] ή πνμζθένμκηαξ εθθζπείξ πθδνμθμνίεξ, ηονίςξ θυβς έθθεζρδξ ακηζπνμζςπεοηζηχκ απεζημκζζηζηχκ δεδμιέκςκ [156][157] ή ηαζ ζε ιενζηέξ πενζπηχζεζξ παναπθακδηζηά υπςξ π.π ζηδκ πενίπηςζδ απυζονζδξ ειπμνζημφ ακηζζχιαημξ [107].…”