The cholinergic anti-inflammatory system limits T cell infiltration into the neurodegenerative CNS, but cannot counteract complex CNS inflammation.
Stimulation of the nicotinic alpha7 acetylcholine receptor (nAChRalpha7) by nicotine or acetylcholine initiates the cholinergic anti-inflammatory pathway, a mechanism for neural inhibition of inflammation. The action of this pathway was initially discovered in animal models of endotoxemia and septic shock, and later described in a number of other diseases. Moreover, the action of this pathway is also implied in human degenerative diseases of the central nervous system (CNS) like amyotrophic lateral sclerosis or Alzheimer's disease. In spite of this general interest, little is known about its involvement in regulating T cell entry into, or inflammatory reactions within the CNS. We tested the action of the cholinergic anti-inflammatory pathway in nAChRalpha7-deficient mice and their wildtype counterparts in two different experimental settings: In the facial nerve axotomy model characterized by neurodegeneration and T cell infiltration, and in the experimental autoimmune encephalomyelitis (EAE) model providing a very complex scenario of CNS inflammation and demyelination. We found that the cholinergic anti-inflammatory pathway limits the site-directed influx of activated T cells into the lesioned facial motor nucleus, but cannot counteract CNS inflammation in EAE.
Medical University Vienna, Center for Brain Research, Department of Neuroimmunology, Spitalgasse 4, Vienna, Austria.
Eva-Maria
EM
Nicolussi
Sigismund
S
Huck
Hans
H
Lassmann
Monika
M
Bradl
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005155:Facial Nerve Diseases / Q000473:pathology*; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000943:Antigens, Differentiation; D017252:CD3 Complex; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D016207:Cytokines; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C036763:monocyte-macrophage differentiation antigen; D052247:Nitric Oxide Synthase Type II; D000109:Acetylcholine