Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: Implications for systemic disease and immunosenescence

Kim, Hyon-Jeen; Barajas, Berenice; Chan, Roger W.; Nel, André E.

doi:10.1016/j.jaci.2007.01.016

Cited by 97 publications

(82 citation statements)

References 29 publications

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“…With respect to the impact of NAC on cell-mediated immunity-the efficiency of which typically declines with aging-there is evidence that glutathione is crucially important to efficient function of dendritic cells, the central coordinators of cell-mediated immunity (Kim et al 2007). Moreover, administration of NAC to aging mice has been shown to restore the delayed-type hypersensitivity to more youthful levels, in precise parallel to the findings of the Italian clinical trial with NAC (Kim et al 2008).…”

Section: Supplemental Nac In Aging Humans and Rodents Provides Versatmentioning

confidence: 99%

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

McCarty

DiNicolantonio

2015

AGE

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Restricted dietary intakes of protein or essential amino acids tend to slow aging and boost lifespan in rodents, presumably because they downregulate IGF-I/ Akt/mTORC1 signaling that acts as a pacesetter for aging and promotes cancer induction. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III cohort has revealed that relatively low protein intakes in mid-life (under 10 % of calories) are indeed associated with decreased subsequent risk for mortality. However, in those over 65 at baseline, such low protein intakes were associated with increased risk for mortality. This finding accords well with other epidemiology correlating relatively high protein intakes with lower risk for loss of lean mass and bone density in the elderly.

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Section: Supplemental Nac In Aging Humans and Rodents Provides Versatmentioning

confidence: 99%

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

McCarty

DiNicolantonio

2015

AGE

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“…Because IL-12 synthesis is modulated by GSH, 10 for which cysteine is limiting, we thought cysteine levels might also impact IL-12 synthesis. We therefore first tested whether SAS, an inhibitor of the cystine X c Ϫ transporter, whose physiologic role is to import cystine, which then converts into cysteine, could mimic the effect of PPG on IL-12 synthesis in DCs.…”

Section: Cse Modulates Il-12 Biosynthesis and Intracellular Cysteine mentioning

confidence: 99%

“…9 In vivo, GSH depletion in antigen-pulsed DCs interferes with the delayed-type hypersensitivity (DTH) response, probably as a consequence of IL-12 repression. 10 H 2 S is the final metabolite of the trans-sulfuration pathway. It is now recognized as the third endogenously produced gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), which induce important physiologic modifications in mammals, such as vasomodulation, synaptic sensitivity, inflammation, and the modulation of immune responses.…”

Section: Introductionmentioning

confidence: 99%

Transplant tolerance is associated with reduced expression of cystathionine-γ-lyase that controls IL-12 production by dendritic cells and TH-1 immune responses

Silly

Coulon

Poirier

et al. 2012

Blood

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AbstractAntigen-activated T lymphocytes undergo an immune or tolerogeneic response in part according to the activation status of their antigen-presenting cells. However, factors controlling the activation of antigen-presenting cells are not fully understood. In this study, we demonstrate that immune tolerance after organ allotransplantation in the rat is associated with a repressed intragraft expression of several enzymes of the trans-sulfuration pathway, including cystathionine γ-lyase (CSE). The pharmacologic blockade of CSE with propargylglycine delayed heart allograft rejection and abrogated type IV hypersensitivity but did not modify antibody responses, and was associated with a selective inhibition of the TH-1 type factors T-bet, IL-12, and IFN-γ. IL-12 repression could also be induced by propargylglycine in vitro in monocytes and dendritic cells (DCs), a phenomenon not mediated by changes to nuclear factor-κ B or hydrogen sulfide but that occurred together with a modulation of intracellular cysteine content. Intracellular cysteine levels were predominantly controlled in DCs by CSE activity, together with extracellular import via the Xc− transporter. Our results indicate that CSE plays a critical role in regulating IL-12 in monocytes and DCs and is down-modulated in transplant tolerance, presumably participating in the maintenance of the tolerant state.

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“…The net effect may be enhanced Th2 responsiveness to environmental allergens. The effect of oxidative stress on DC function has been confirmed by in vivo murine studies employing glutathione depletion by systemic diethyl maleate [35]. This oxidative stress challenge interferes with IL-12 production and costimulatory receptor expression in DC, and reduces skin IFNproduction and delayed-type hypersensitivity responses to contact-sensitizing antigens.…”

Section: Molecular Mechanisms Of Pollutant Proallergic Effectsmentioning

confidence: 89%

The effect of air pollution on asthma and allergy

Riedl

2008

Curr Allergy Asthma Rep

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Air pollution exposure is associated with increased asthma and allergy morbidity and is a suspected contributor to the increasing prevalence of allergic conditions. Observational studies continue to strengthen the association between air pollution and allergic respiratory disease, whereas recent mechanistic studies have defined the prominent role of oxidative stress in the proallergic immunologic effects of particulate and gaseous pollutants. The identification of common genetic polymorphisms in key cytoprotective responses to oxidative stress has highlighted the importance of individual host susceptibility to pollutant-induced inflammation. Future therapy to reduce the adverse effects of air pollution on allergic respiratory disease will likely depend on targeting susceptible populations for treatment that reduces oxidative stress, potentially through enhancement of phase 2 enzymes or other antioxidant defenses.

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Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: Implications for systemic disease and immunosenescence

Cited by 97 publications

References 29 publications

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

Transplant tolerance is associated with reduced expression of cystathionine-γ-lyase that controls IL-12 production by dendritic cells and TH-1 immune responses

The effect of air pollution on asthma and allergy

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