Chronic Inflammation in Immune Aging: Role of Pattern Recognition Receptor Crosstalk with the Telomere Complex?

Jose, Shyam Sushama; Bendíčková, Kamila; Kepák, Tomáš; Křenová, Zdenka; Frič, Jan

doi:10.3389/fimmu.2017.01078

Cited by 86 publications

(60 citation statements)

References 165 publications

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“…Some of the cytokines attract cells of the innate immune system (such as neutrophils, macrophages, and dendritic cells) and result in a persistent inflammatory response in COPD 52 , 53 . Earlier evidence shows a close relationship between the activation of PRR pathways and inflammaging 54 – 56 . However, it remains unclear how DAMPs markers play a vital role during aging and aging-associated chronic inflammatory lung diseases.…”

Section: Discussionmentioning

confidence: 92%

Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema

Rashid

Sundar

Gerloff

et al. 2018

Sci Rep

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Cigarette smoke (CS) induces lung cellular senescence that plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). How aging influences cellular senescence and other molecular hallmarks, and increases the risk of CS-induced damage remains unknown. We hypothesized that aging-associated changes in lungs worsen the COPD/emphysema by CS exposure. Younger and older groups of C57BL/6J mice were exposed to chronic CS for 6 months with respective age-matched air-exposed controls. CS caused a decline in lung function and affected the lung structure of both groups of mice. No alterations were observed in the induction of inflammatory mediators between the air-exposed younger and older controls, but aging increased the severity of CS-induced lung inflammation. Aging per se increased lung cellular senescence and significant changes in damage-associated molecular patterns marker S100A8. Gene transcript analysis using the nanoString nCounter showed a significant upregulation of key pro-senescence targets by CS (Mmp12, Ccl2, Cdkn2a, Tert, Wrn, and Bub1b). Aging independently influenced lung function and structure, as well as increased susceptibility to CS-induced inflammation in emphysema, but had a negligible effect on cellular senescence. Thus, aging solely does not contribute to the induction of cellular senescence by CS in a mouse model of COPD/emphysema.

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Section: Discussionmentioning

confidence: 92%

Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema

Rashid

Sundar

Gerloff

et al. 2018

Sci Rep

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“…( 37 )]. Indeed, some of the prominent features of immunosenescence are inflammation, decreased T cell numbers, and decreased naïve and memory T cell responsiveness ( 37 , 38 , 39 ), and in the aged, inflammaging can contribute to dysregulated DC responses and a consequent breakdown of tolerance that can predispose them to autoimmunity ( 40 , 41 ). We propose that in this context, modest elevation of CRP due to biological aging ( 12 ) might act as a tonic suppressor of DC activation and thus limit auto-reactivity.…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance

et al. 2018

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C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE) in CRP transgenic mice by shifting CD4+ T cells away from the TH1 and toward the TH2 subset. Notably, this action required the inhibitory Fcγ receptor IIB (FcγRIIB), but did not require high levels of human CRP. Herein, we sought to determine if CRP’s influence in EAE might be explained by CRP acting on dendritic cells (DC; antigen presenting cells known to express FcγRIIB). We found that CRP (50 µg/ml) reduced the yield of CD11c+ bone marrow-derived DCs (BMDCs) and CRP (≥5 μg/ml) prevented their full expression of major histocompatibility complex class II and the co-stimulatory molecules CD86 and CD40. CRP also decreased the ability of BMDCs to stimulate antigen-driven proliferation of T cells in vitro. Importantly, if the BMDCs were genetically deficient in mouse FcγRIIB then (i) the ability of CRP to alter BMDC surface phenotype and impair T cell proliferation was ablated and (ii) CD11c-driven expression of a human FCGR2B transgene rescued the CRP effect. Lastly, the protective influence of CRP in EAE was fully restored in mice with CD11c-driven human FcγRIIB expression. These findings add to the growing evidence that CRP has important biological effects even in the absence of an acute phase response, i.e., CRP acts as a tonic suppressor of the adaptive immune system. The ability of CRP to suppress development, maturation, and function of DCs implicates CRP in the maintenance of peripheral T cell tolerance.

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“…Consequently, blood samples from the patients were drawn at a time when medical treatment, stress, and inflammatory conditions may have had an effect on rLTL in peripheral blood. But, since stress and inflammatory conditions are expected to shorten telomere length in patients [41], these confounding factors would not affect the association between longer telomere length and glioma risk.…”

Section: Discussionmentioning

confidence: 99%

The association between longer relative leukocyte telomere length and risk of glioma is independent of the potentially confounding factors allergy, BMI, and smoking

Andersson

Degerman

Dahlin

et al. 2018

Cancer Causes Control

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Purpose Previous studies have suggested an association between relative leukocyte telomere length (rLTL) and glioma risk. This association may be influenced by several factors, including allergies, BMI, and smoking. Previous studies have shown that individuals with asthma and allergy have shortened relative telomere length, and decreased risk of glioma. Though, the details and the interplay between rLTL, asthma and allergies, and glioma molecular phenotype is largely unknown. Methods rLTL was measured by qPCR in a Swedish population-based glioma case-control cohort (421 cases and 671 controls). rLTL was related to glioma risk and health parameters associated with asthma and allergy, as well as molecular events in glioma including IDH1 mutation, 1p/19q co-deletion, and EGFR amplification. Results Longer rLTL was associated with increased risk of glioma (OR = 1.16; 95% CI 1.02-1.31). Similar to previous reports, there was an inverse association between allergy and glioma risk. Specific, allergy symptoms including watery eyes was most strongly associated with glioma risk. High body mass index (BMI) a year prior diagnosis was significantly protective against glioma in our population. Adjusting for allergy, asthma, BMI, and smoking did not markedly change the association between longer rLTL and glioma risk. rLTL among cases was not associated with IDH1 mutation, 1p/19q codeletion, or EGFR amplification, after adjusting for age at diagnosis and sex. Conclusions In this Swedish glioma case-control cohort, we identified that long rLTL increases the risk of glioma, an association not confounded by allergy, BMI, or smoking. This highlights the complex interplay of the immune system, rLTL and cancer risk.Keywords Glioma · Relative leukocyte telomere length (rLTL) · Allergy · BMI · Smoking · IDH1 · 1p/19q · EGFR Electronic supplementary material The online version of this article (https ://doi.

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Chronic Inflammation in Immune Aging: Role of Pattern Recognition Receptor Crosstalk with the Telomere Complex?

Cited by 86 publications

References 165 publications

Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema

Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema

C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance

The association between longer relative leukocyte telomere length and risk of glioma is independent of the potentially confounding factors allergy, BMI, and smoking

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