Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease

Marina Saresella, Elena Calabrese, Ivana Marventano, Federica Piancone, Andrea Gatti, Margherita Alberoni, Raffaello Nemni, Mario Clerici

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)539-547
Number of pages9
JournalBrain, Behavior, and Immunity
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Alzheimer's disease
  • Memory/naïve lymphocytes
  • Neuroinflammation
  • T helper lymphocytes
  • Th-17
  • Th-9

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

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