Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes

Mansfield, Aaron S.; Nevala, Wendy K.; Dronca, Roxana S.; Leontovich, Alexey A.; Shuster, Lynne T.; Markovic, S. N.

doi:10.1111/j.1365-2249.2012.04644.x

Cited by 64 publications

(42 citation statements)

References 38 publications

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“…Thus, the differences in proportions for these 2 subsets between the ueRA and HC groups may not be attributable to age, because there was no significant difference between the ages of patients with ueRA and HC subjects in our study. The increase in Th2 cells with age has also been reported in healthy individuals [48]. As the prevalence of RA increases with age [49], it is therefore possible that the higher burden of Th2 cells in the circulation puts older individuals at higher risk of developing RA than younger ones.…”

Section: Discussionmentioning

confidence: 95%

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Pandya

Lundell

Hallström

et al. 2016

Journal of Leukocyte Biology

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The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25 CD127 and also FOXP3 CXCR5 cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4CXCR3 (Th2 and Th17), CTLA4 and FOXP3 subsets were present in significantly higher frequencies, whereas CCR4 (Th1/Th17, CCR6CCR4CXCR3, and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4CXCR3 T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.

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Section: Discussionmentioning

confidence: 95%

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Pandya

Lundell

Hallström

et al. 2016

Journal of Leukocyte Biology

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“…Our data suggest that these cytokines play important roles in cardiac aging. In support, plasma monocyte chemotactic protein-1 and Ccl5 have been reported to be increased with age in healthy subjects (36).…”

Section: Ccl5 (M1)mentioning

confidence: 88%

Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization

Toba

Brás

Baicu

et al. 2015

American Journal of Physiology-Cell Physiology

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Toba H, de Castro Brás LE, Baicu CF, Zile MR, Lindsey ML, Bradshaw AD. Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization. Am J Physiol Cell Physiol 308: C972-C982, 2015. First published April 15, 2015; doi:10.1152/ajpcell.00402.2014.-To investigate the role of secreted protein acidic and rich in cysteine (SPARC) in age-related cardiac inflammation, we studied six groups of mice: young (3-5 mo old), middle-aged (10 -12 mo old), and old (18 -29 mo old) C57BL/6 wild-type (WT) and SPARC-null (Null) mice (n ϭ 7-10/group). Cardiac function and structure were determined by echocardiography. The left ventricle was used for cytokine gene array and macrophage quantification by immunohistochemistry. Macrophage infiltration increased with age in WT (n ϭ 5-6/group, P Ͻ 0.05 for young vs. old), but not in Null. Proinflammatory markers (Ccl5, Cx3cl1, Ccr2, and Cxcr3) increased in middle-aged and old WT, whereas they were increased only in old Null compared with respective young (n ϭ 5-6/group, P Ͻ 0.05 for all). These results suggest that SPARC deletion delayed age-related cardiac inflammation. To further assess how SPARC affects inflammation, we stimulated peritoneal macrophages with SPARC (n ϭ 4). SPARC treatment increased expression of proinflammatory macrophage M1 markers and decreased anti-inflammatory M2 markers. Echocardiography (n ϭ 7-10/group) revealed an age-related increase in wall thickness of the left ventricle in WT (0.76 Ϯ 0.02 mm in young vs. 0.91 Ϯ 0.03 mm in old; P Ͻ 0.05) but not in Null (0.78 Ϯ 0.01 mm in young vs. 0.84 Ϯ 0.02 mm in old). In conclusion, SPARC deletion delayed age-related increases in macrophage infiltration and proinflammatory cytokine expression in vivo and in vitro. SPARC acts as an important mediator of age-related cardiac inflammation by increasing the expression of macrophage M1 markers and decreasing M2 markers.

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“…The immune response in the old skin is skewed toward a Th2-suppressive mode, including elevated levels of IL10 and IL4 and accumulation of mast cells. 62 Following TCR activation in aged mice, naive CD4 + T cells differentiate toward a Th2 fate. 63 Chronic Th2 inflammation is pernicious, as it recruits mast cells and eosinophils, both ECM modulators that can mediate tissue destruction and support tumor growth, 64,65 although in c-Kit − / − mice mast cells can actually confer tumor protection.…”

Section: Discussionmentioning

confidence: 99%

Age-associated inflammation connects RAS-induced senescence to stem cell dysfunction and epidermal malignancy

et al. 2015

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Aging is the single biggest risk factor for malignant transformation. Among the most common age-associated malignancies are non-melanoma skin cancers, comprising the most common types of human cancer. Here we show that mutant H-Ras activation in mouse epidermis, a frequent event in cutaneous squamous cell carcinoma (SCC), elicits a differential outcome in aged versus young mice. Whereas H-Ras activation in the young skin results in hyperplasia that is mainly accompanied by rapid hair growth, H-Ras activation in the aged skin results in more dysplasia and gradual progression to in situ SCC. Progression is associated with increased inflammation, pronounced accumulation of immune cells including T cells, macrophages and mast cells as well as excessive cell senescence. We found not only an age-dependent increase in expression of several pro-inflammatory mediators, but also activation of a strong anti-inflammatory response involving enhanced IL4/IL10 expression and immune skewing toward a Th2 response. In addition, we observed an age-dependent increase in the expression of Pdl1, encoding an immune suppressive ligand that promotes cancer immune evasion. Moreover, upon switching off oncogenic H-Ras activity, young but not aged skin regenerates successfully, suggesting a failure of the aged epidermal stem cells to repair damaged tissue. Our findings support an age-dependent link between accumulation of senescent cells, immune infiltration and cancer progression, which may contribute to the increased cancer risk associated with old age.

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Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes

Cited by 64 publications

References 38 publications

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization

Age-associated inflammation connects RAS-induced senescence to stem cell dysfunction and epidermal malignancy

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