Aging is associated with circulating cytokine dysregulation

Álvarez-Rodríguez, Lorena; López-Hoyos, Marcos; Muñoz-Cacho, Pedro; Martínez‐Taboada, Víctor M.

doi:10.1016/j.cellimm.2012.01.001

Cited by 160 publications

(129 citation statements)

References 34 publications

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“…6G,H). Overall, our data suggest that age‐associated Tim‐3 + PD‐1 + CD8 + T cells produce high levels of IL‐10 and have potential to promote the IL‐10‐dependent expression of IL‐10 in normal CD8 + T cells and that these activities may contribute to the increased levels of IL‐10 in the aged immune system (Spencer et al ., 1996; Alvarez‐Rodriguez et al ., 2012). …”

Section: Resultsmentioning

confidence: 99%

“…For instance, IL‐10 inhibits the priming of CD8 + T cells but stimulates activated CD8 + T cells in vivo (Emmerich et al ., 2012). Of note, the production of IL‐10 has been shown to be elevated in both human and mice with aging (Spencer et al ., 1996; Alvarez‐Rodriguez et al ., 2012), which is considered to involve aging‐related attenuated immune responses, and it has also been shown that aged CD44 hi CD8 + T cells express IL‐10 (Decman et al ., 2012). Our observations suggest that the Tim‐3 + PD‐1 + population is the main source of IL‐10 production in CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of age‐associated exhausted CD8⁺ T cells defined by increased expression of Tim‐3 and PD‐1

et al. 2016

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SummaryAging is accompanied by altered T‐cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (PD‐1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T‐cell exhaustion and aging‐associated immune dysfunction. In this study, we demonstrate that T‐cell immunoglobulin mucin domain‐3 (Tim‐3), another exhaustion marker, is up‐regulated on aged T cells, especially CD8+ T cells. Tim‐3‐expressing cells also produced PD‐1, but Tim‐3+ PD‐1+ CD8+ T cells had a distinct phenotype that included the expression of CD44 and CD62L, from Tim‐3− PD‐1+ cells. Tim‐3+ PD‐1+ CD8+ T cells showed more evident properties associated with exhaustion than Tim‐3− PD‐1+ CD8+ T cells: an exhaustion‐related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL‐10 and induced normal CD8+ T cells to produce IL‐10, which might contribute to immune dysregulation in aged mice. The generation of Tim‐3‐expressing CD8+ T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD8+ T‐cell population with age‐associated exhaustion was distinguishable by its expression of Tim‐3. These results provide clues for understanding the alterations that occur in T‐cell populations with age and for improving dysfunctions related to the aging of the immune system.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of age‐associated exhausted CD8⁺ T cells defined by increased expression of Tim‐3 and PD‐1

et al. 2016

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“…We have recently demonstrated that elevated myostatin and elevated SC-specific myostatin levels in type II SCs may be one of the key factors impairing the myogenic capacity of muscle in older humans (37). Although elevated myostatin appears to be, in part, responsible for the age-related SC dysfunction, aging is also associated with higher muscle SOCS3 protein and circulating inflammatory cytokines such as IL-6 and IL-1␤ (30,57). Currently, it is unclear if these are mutually exclusive or are related processes.…”

Section: Discussionmentioning

confidence: 99%

“…However, the appearance of elevated IL-6 was transient, with SOCS3 mRNA being induced rapidly (24 h) following muscle damage, likely to inhibit the STAT3 cascade and limit proliferation to allow for differentiation to begin (18,35,56). In healthy older humans, IL-6 has been shown to be chronically elevated (57), which may impair the normal IL-6 response and the sensitivity of the SCs to IL-6.…”

Section: Discussionmentioning

confidence: 99%

“…Human studies have demonstrated strong associations between elevated serum IL-6 and lower muscle strength and muscle mass associated with the aging process (47,60). Furthermore, it appears that systemic IL-6 is elevated in healthy older (70.6 Ϯ 7.9 yr) individuals (57), suggesting IL-6 is increased as a consequence of normal human aging. Although the exact mechanisms detailing how chronically elevated IL-6 promotes muscle catabolism remain unclear, the role of SOCS proteins has been implicated in reducing the efficacy of anabolic signaling pathways such as IGF-1 in skeletal muscle (1).…”

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confidence: 99%

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Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

McKay

Ogborn

Baker

et al. 2013

American Journal of Physiology-Cell Physiology

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Adaptive Immunity and Metabolic Health: Harmony Becomes Dissonant in Obesity and Aging

Bharath

Nikolajczyk³

2017

Comprehensive Physiology

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Adipose tissue (AT) is the primary energy reservoir organ, and thereby plays a critical role in energy homeostasis and regulation of metabolism. AT expands in response to chronic overnutrition or aging and becomes a major source of inflammation that has marked influence on systemic metabolism. The chronic, sterile inflammation that occurs in the AT during the development of obesity or in aging contributes to onset of devastating diseases such as insulin resistance, diabetes, and cardiovascular pathologies. Numerous studies have shown that inflammation in the visceral AT of humans and animals is a critical trigger for the development of metabolic syndrome. This work underscores the well-supported conclusion that the inflammatory immune response and metabolic pathways in the AT are tightly interwoven by multiple layers of relatively conserved mechanisms. During the development of diet-induced obesity or age-associated adiposity, cells of the innate and the adaptive immune systems infiltrate and proliferate in the AT. Macrophages, which dominate AT-associated immune cells in mouse models of obesity, but are less dominant in obese people, have been studied extensively. However, cells of the adaptive immune system, including T cells and B cells, contribute significantly to AT inflammation, perhaps more in humans than in mice. Lymphocytes regulate recruitment of innate immune cells into AT, and produce cytokines that influence the helpful-to-harmful inflammatory balance that, in turn, regulates organismal metabolism. This review describes inflammation, or more precisely, metabolic inflammation (metaflammation) with an eye toward the AT and the roles lymphocytes play in regulation of systemic metabolism during obesity and aging. © 2017 American Physiological Society. Compr Physiol 7:1307-1337, 2017.

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Aging is associated with circulating cytokine dysregulation

Cited by 160 publications

References 34 publications

Characterization of age‐associated exhausted CD8⁺ T cells defined by increased expression of Tim‐3 and PD‐1

Characterization of age‐associated exhausted CD8⁺ T cells defined by increased expression of Tim‐3 and PD‐1

Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

Adaptive Immunity and Metabolic Health: Harmony Becomes Dissonant in Obesity and Aging

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Aging is associated with circulating cytokine dysregulation

Cited by 160 publications

References 34 publications

Characterization of age‐associated exhausted CD8+ T cells defined by increased expression of Tim‐3 and PD‐1

Characterization of age‐associated exhausted CD8+ T cells defined by increased expression of Tim‐3 and PD‐1

Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

Adaptive Immunity and Metabolic Health: Harmony Becomes Dissonant in Obesity and Aging

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Characterization of age‐associated exhausted CD8⁺ T cells defined by increased expression of Tim‐3 and PD‐1

Characterization of age‐associated exhausted CD8⁺ T cells defined by increased expression of Tim‐3 and PD‐1