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

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

doi:10.1016/j.bbi.2010.12.004

Cited by 150 publications

(112 citation statements)

References 66 publications

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“…In addition, changes in lymphocyte subsets have been observed in patients with mild cognitive impairment and Alzheimer's disease. Patients with mild cognitive impairment or Alzheimer's disease showed lower percentages of B cells [28,47] but increased expansion of late-differentiated T cells (CD28-), especially in CD4+ cells [48,49,50]. These data are in line with our findings and give further support to the role of peripheral lymphocytes in human cognition.…”

Section: Discussionsupporting

confidence: 82%

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

Petersen

Grassi‐Oliveira

Siara

et al. 2014

Neuroimmunomodulation

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Background: Rheumatoid arthritis (RA) has been associated with premature immunosenescence and an increased prevalence of age-related morbidities including poor cognitive function. Objective: We explored the relationships among lymphocyte subsets and memory in RA. Methods: Thirty patients with RA and 19 age-matched healthy controls took part in this study. Cognitive function stress and depression scores were evaluated by structured clinical questionnaires. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate the following subsets: B cells, activated and naïve/memory T cells, regulatory FoxP3+ T (Treg) cells, Th17+ cells, NK cells and senescence-associated CD28- T cells. Results: RA patients were more depressed than controls, but stress levels were similar in the 2 groups. Patients had impaired memory performance compared to controls, demonstrated by lower Mini-Mental State Examination scores and logical and working memories (all p < 0.0001). These group effects remained significant after correcting for depression and age. Patients had expansion of regulatory T cells, naïve CD4+ T cells and CD8+CD28- cells but reduced percentages of B cells and memory CD8+CD45RO+ T cells compared to controls. CD8+CD28- and CD8+CD45RO+ T cells were found to be negatively associated with memory. Conclusion: RA patients had reduced memory performance compared to healthy controls. Expansion of activated and senescence-associated T cells was correlated with poor memory performance.

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Section: Discussionsupporting

confidence: 82%

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

Petersen

Grassi‐Oliveira

Siara

et al. 2014

Neuroimmunomodulation

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“…IL-23 not only synergizes with IL-6 and IL-1 to promote Th17 development, but also stimulates Th17 expansion and prolongs IL-17 production [17,18,19]. Recent reports also show that Th17 cell-mediated neuroinflammation is involved in the pathogenesis of various chronic inflammatory conditions including atherosclerosis and AD [14,20,21]. Furthermore, cholesterol accelerates atherosclerosis via the alternative IL-23/Th17 pathway in IL-18 deficiency, demonstrating a new role for Th17 in chronic inflammation [20].…”

Section: Introductionmentioning

confidence: 99%

“…Deposition of fibrillar Aβ was seen in AD [22], and both Th17 and IL-23 were augmented in AD patients upon in vitro stimulation of cells with Aβ [21]. IL-18 has been implicated in the pathogenesis of AD [6,8,11], and IL-18 can combine with IL-23 to stimulate the IL-17 production in experimental autoimmune encephalomyelitis (EAE) [23].…”

Section: Introductionmentioning

confidence: 99%

“…IL-18 has been implicated in the pathogenesis of AD [6,8,11], and IL-18 can combine with IL-23 to stimulate the IL-17 production in experimental autoimmune encephalomyelitis (EAE) [23]. The IL-23/Th17 axis plays a role in AD-associated neuroinflammation [21], and IL-17 in the production of Th17. Therefore, there may be some relationships among IL-18, IL-23 and IL-17 in the etiopathogenesis of AD.…”

Section: Introductionmentioning

confidence: 99%

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Increased Serum Levels of Interleukin-18, -23 and -17 in Chinese Patients with Alzheimer's Disease

Chen

Jiang

et al. 2014

Dement Geriatr Cogn Disord

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Aims: To evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with Alzheimer's disease (AD), and explore correlations between the three cytokines and relevant parameters. Methods: Serum concentrations of IL-18, IL-23 and IL-17 were measured by ELISA for 53 AD patients and 53 sex- and age-matched healthy controls in a community of elderly individuals in a Shanghai suburb. Results: Serum concentrations of IL-18, IL-23 and IL-17 were significantly higher in AD patients than controls. The serum level of IL-23 was observed to be significantly higher (p = 0.049) in female AD patients than male AD patients. In addition, a significantly inverse correlation was found between IL-18 and MMSE score (r_s = -0.356, p = 0.011) for all AD patients. Conclusion: Elevated IL-18, IL-23 and IL-17 levels are observed in AD patients and differences may exist between males and females. Besides, IL-18 may correlate with the severity of AD.

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“…The weight of evidence indicates that CD4 T cells are activated and highly differentiated in AD patients as indicated by a reduction in naïve and central memory CD4 + T cells, an increase in Th17 T cells and a reduction in regulatory T cells (Tregs) [34,81,82]. In addition, the pattern of receptor distribution on the surface of CD4 T cells may also differ between AD patients and age-and sex-matched controls, with an increased number of CD4 + CD28 − cells being reported [34].…”

Section: Evidence Of Peripheral Immune Abnormalities In Admentioning

confidence: 99%

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

et al. 2018

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The classical amyloid cascade model for Alzheimer's disease (AD) has been challenged by several findings. Here, an alternative molecular neurobiological model is proposed. It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD. In particular, as a result of increased activity of triggering receptor expressed on myeloid cells 2 (TREM-2), the presence of the apolipoprotein E4 (ApoE4) isoform, and changes in ANK1 expression, with subsequent changes in miR-486 leading to altered levels of protein kinase B (Akt), mechanistic (previously mammalian) target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), all of which play major roles in microglial activation, proliferation and survival, there is activation of microglia, leading to the subsequent (further) production of cytokines, chemokines, nitric oxide, prostaglandins, reactive oxygen species, inducible nitric oxide synthase and cyclooxygenase-2, and other mediators of inflammation and neurotoxicity. These changes are associated with the development of amyloid and tau pathology, mitochondrial dysfunction (including impaired activity of the electron transport chain, depleted basal mitochondrial potential and oxidative damage to key tricarboxylic acid enzymes), synaptic dysfunction, altered glycogen synthase kinase-3 (GSK-3) activity, mTOR activation, impairment of autophagy, compromised ubiquitin-proteasome system, iron dyshomeostasis, changes in APP translation, amyloid plaque formation, tau hyperphosphorylation and neurofibrillary tangle formation.

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

Cited by 150 publications

References 66 publications

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

Premature Immunosenescence Is Associated with Memory Dysfunction in Rheumatoid Arthritis

Increased Serum Levels of Interleukin-18, -23 and -17 in Chinese Patients with Alzheimer's Disease

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

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