title: Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease.
abstract: Inflammatory mediators are responsible for the neuroinflammation observed in Alzheimer's disease (AD), a phenomenon that might be the culprit of disease or, possibly, a reaction to pathology. To better investigate inflammation in AD we performed an extensive immunophenotypic and functional analysis of amyloid-beta (Aβ) stimulated T lymphocytes in patients with a diagnosis of AD comparing data to those obtained in individuals with mild cognitive impairment (MCI) or aged-matched healthy individuals (HC). Results showed that IL-21- and IL-9-producing Aβ stimulated CD4(+) T cells, as well as IL-23- and IL-6-producing monocytes and CD4(+) T cells expressing the RORγ and NFATc1 transcriptional factors (TF), were significantly increased, whereas IL-10-producing monocytes were decreased in AD. Notably, GATA-3 TF-expressing CD4(+) T lymphocytes were significantly increased in MCI alone. Analysis of the post-thymic differentiation pathway indicated that Aβ specific naïve and central memory CD4(+) T lymphocytes were diminished whereas effector memory and terminally differentiated CD4(+) T lymphocytes were increased in AD and MCI compared to HC. Data herein indicate that cytokines (IL-21, IL-6, IL-23) and TF (RORγ) involved in the differentiation of Th-17 cells), as well as cytokines (IL-21, IL-22) generated by such cells, and IL-9, produced by Th-9 cells, are significantly increased in AD. This is accompanied by a shift of post-thymic differentiation pathways favoring the accumulation of differentiated, effector T lymphocytes. These data shed light on the nature of AD-associated neuroinflammation. A better understanding of the complexity of this phenomenon could facilitate the search for novel therapeutic strategies.
authors.affiliation: Laboratory of Molecular Medicine and Biotechnology, IRCCS S. Maria Nascente, Don C. Gnocchi ONLUS Foundation, Via Capecelatro 66, Milano 20148, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.forename: Elena
authors.initials: E
authors.lastname: Calabrese
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.forename: Federica
authors.initials: F
authors.lastname: Piancone
authors.forename: Andrea
authors.initials: A
authors.lastname: Gatti
authors.forename: Margherita
authors.initials: M
authors.lastname: Alberoni
authors.forename: Raffaello
authors.initials: R
authors.lastname: Nemni
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation; D003072:Cognition Disorders / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D007378:Interleukins / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D016229:Amyloid beta-Peptides; D007378:Interleukins