期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 25, 期 3, 页码 539-547出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2010.12.004
关键词
Alzheimer's disease; Neuroinflammation; T helper lymphocytes; Th-17; Th-9; Memory/naive lymphocytes
资金
- Istituto Superiore di Sanita'
- EMPRO
- AVIP EC
- nGIN EC
- Japan Health Science Foundation
- Italian Ministry of Health
- Fondazione Cariplo
- Rete Italiana Chimica Farmaceutica CHEM-PROFARMA-NET [RBPR05NWWC]
- progetto FIRB RETI
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 (A beta) 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 A beta stimulated CD4(+) T cells, as well as IL-23- and IL-6-producing monocytes and CE4(+) T cells expressing the ROR gamma and NFATc1 transcriptional factors (IF), were significantly increased, whereas IL-10-producing monocytes were decreased in AD. Notably, GATA-3 IF-expressing CD4(+) T lymphocytes were significantly increased in MCI alone. Analysis of the post-thymic differentiation pathway indicated that All specific naive 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 (ROR gamma) 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. (C) 2010 Elsevier Inc. All rights reserved.
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