title: Cholinergic regulatory lymphocytes re-establish neuromodulation of innate immune responses in sepsis.
abstract: Many anti-inflammatory strategies that are successful in treating sepsis in healthy animals fail in clinical trials, in part because sepsis normally involves immunocompromised patients, and massive lymphocyte apoptosis prevents immunomodulation. In this article, we report a new set of regulatory lymphocytes that are able to re-establish the cholinergic anti-inflammatory modulation and to provide therapeutic advantages in sepsis. The vagus nerve controls inflammation in healthy, but not in septic, mice. Likewise, vagus nerve and cholinergic agonists fail to control inflammation in splenectomized and nude animals. Unlike typical suppressor CD25(+) cells, CD4(+)CD25(-) lymphocytes re-establish the anti-inflammatory potential of the vagus nerve and cholinergic agonists in immunocompromised and septic animals. These cholinergic lymphocytes re-establish splenic protection and the potential of cholinergic agonists to rescue immunocompromised animals from established sepsis. The study results revealed these new regulatory lymphocytes as, to our knowledge, the first known physiological target for neuromodulation of the innate immune responses and a potential therapeutic target for sepsis.
authors.affiliation: Laboratory of Immunity and Infection, Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Geber
authors.initials: G
authors.lastname: Peña
authors.forename: Bolin
authors.initials: B
authors.lastname: Cai
authors.forename: Laura
authors.initials: L
authors.lastname: Ramos
authors.forename: Gergely
authors.initials: G
authors.lastname: Vida
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Luis
authors.initials: L
authors.lastname: Ulloa
mesh_terms: D000818:Animals; D002432:Cecum; D019446:Endotoxemia / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D007113:Immunity, Innate; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D015213:Neuroimmunomodulation / Q000276:immunology*; D011677:Punctures; D011897:Random Allocation; D011978:Receptors, Nicotinic / Q000502:physiology*; D018805:Sepsis / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014630:Vagus Nerve / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor