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.
Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease / M. Saresella, E. Calabrese, I. Marventano, F. Piancone, A. Gatti, M. Alberoni, R. Nemni, M.S. Clerici. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 25:3(2011 Mar), pp. 539-547.
|Titolo:||Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer's disease|
NEMNI, RAFFAELLO (Penultimo)
CLERICI, MARIO SALVATORE (Ultimo)
|Parole Chiave:||Alzheimer's disease; Memory/naïve lymphocytes; Neuroinflammation; T helper lymphocytes; Th-17; Th-9|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
Settore MED/26 - Neurologia
|Data di pubblicazione:||mar-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bbi.2010.12.004|
|Appare nelle tipologie:||01 - Articolo su periodico|