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2020-05-04
Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: Implications for systemic disease and immunosenescence
Source (資訊來源):
https://www.jacionline.org/article/S0091-6749(07)00177-7/fulltext
Info cited on 2020-05-04-WD1 (資訊引用於 中華民國109年5月4日) by 湯偉晉 (WeiJin Tang)
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BASIC AND CLINICAL IMMUNOLOGY| VOLUME 119, ISSUE 5, P1225-1233, MAY 01, 2007
Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: Implications for systemic disease and immunosenescence
2020-05-04
Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: Implications for systemic disease and immunosenescence
Source (資訊來源):
https://www.jacionline.org/article/S0091-6749(07)00177-7/fulltext
Info cited on 2020-05-04-WD1 (資訊引用於 中華民國109年5月4日) by 湯偉晉 (WeiJin Tang)
#
- - - - - - - -
BASIC AND CLINICAL IMMUNOLOGY| VOLUME 119, ISSUE 5, P1225-1233, MAY 01, 2007
Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: Implications for systemic disease and immunosenescence
Begin_電腦自動翻譯的內容_Y2020m05d04h03m52Rn5980_
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
穀胱甘肽耗竭抑制樹突狀細胞成熟和遲髮型超敏反應：對全身性疾病和免疫衰老的影響
End_電腦自動翻譯的內容_Y2020m05d04h03m52Rn5980_
Hyon-Jeen Kim, PhD
Berenice Barajas, BS
Ray Chun-Fai Chan, PhD
Andre E. Nel, MD, PhD
Published:March 10, 2007DOI:https://doi.org/10.1016/j.jaci.2007.01.016
Background
Dendritic cells (DCs) play a key role as antigen-presenting cells in the immune system. There is growing evidence that the redox equilibrium of these cells influences their ability to induce T-cell activation and to regulate the polarity of the immune response. This could affect the outcome of the immune response during systemic diseases and aging.
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
穀胱甘肽耗竭抑制樹突狀細胞成熟和遲髮型超敏反應：對全身性疾病和免疫衰老的影響
End_電腦自動翻譯的內容_Y2020m05d04h03m52Rn5980_
Hyon-Jeen Kim, PhD
Berenice Barajas, BS
Ray Chun-Fai Chan, PhD
Andre E. Nel, MD, PhD
Published:March 10, 2007DOI:https://doi.org/10.1016/j.jaci.2007.01.016
Background
Dendritic cells (DCs) play a key role as antigen-presenting cells in the immune system. There is growing evidence that the redox equilibrium of these cells influences their ability to induce T-cell activation and to regulate the polarity of the immune response. This could affect the outcome of the immune response during systemic diseases and aging.
Begin_電腦自動翻譯的內容_Y2020m05d04h03m56Rn2887_
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
背景
樹突狀細胞（DC）在免疫系統中作為抗原呈遞細胞發揮著關鍵作用。越來越多的證據表明，這些細胞的氧化還原平衡會影響它們誘導T細胞活化和調節免疫應答極性的能力。這可能會影響全身性疾病和衰老過程中免疫反應的結果。
End_電腦自動翻譯的內容_Y2020m05d04h03m56Rn2887_
Objective
Our aim was to elucidate the mechanism by which the redox equilibrium of antigen-presenting DCs affects the delayed-type hypersensitivity (DTH) response during experimental modification of glutathione levels, as well as during aging.
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
背景
樹突狀細胞（DC）在免疫系統中作為抗原呈遞細胞發揮著關鍵作用。越來越多的證據表明，這些細胞的氧化還原平衡會影響它們誘導T細胞活化和調節免疫應答極性的能力。這可能會影響全身性疾病和衰老過程中免疫反應的結果。
End_電腦自動翻譯的內容_Y2020m05d04h03m56Rn2887_
Objective
Our aim was to elucidate the mechanism by which the redox equilibrium of antigen-presenting DCs affects the delayed-type hypersensitivity (DTH) response during experimental modification of glutathione levels, as well as during aging.
Begin_電腦自動翻譯的內容_Y2020m05d04h03m58Rn5158_
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
目的
我們的目的是闡明在穀胱甘肽水平的實驗性修飾以及衰老過程中，抗原呈遞DC的氧化還原平衡影響延遲型超敏反應（DTH）的機制。
End_電腦自動翻譯的內容_Y2020m05d04h03m58Rn5158_
Methods
We looked at the effect of glutathione depletion by diethyl maleate in DCs as well as during systemic administration on the DTH response to the contact-sensitizing antigens, oxazolone, and 2,4-dinitro-1-fluorobenzene. We also determined whether glutathione repletion with N-acetyl cysteine could influence the decline of the DTH response in aged mice.
Results
Glutathione depletion in bone marrow–derived DCs interfered in their ability to mount a DTH response on adoptive transfer into recipient mice. Glutathione depletion interfered in IL-12 production and costimulatory receptor expression in DCs, leading to decreased IFN-γ production in the skin of recipient mice. Systemic diethyl maleate treatment exerted similar effects on the DTH response and IFN-γ production, whereas N-acetyl cysteine administration reversed the decline of the DTH response in aged animals.
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
目的
我們的目的是闡明在穀胱甘肽水平的實驗性修飾以及衰老過程中，抗原呈遞DC的氧化還原平衡影響延遲型超敏反應（DTH）的機制。
End_電腦自動翻譯的內容_Y2020m05d04h03m58Rn5158_
Methods
We looked at the effect of glutathione depletion by diethyl maleate in DCs as well as during systemic administration on the DTH response to the contact-sensitizing antigens, oxazolone, and 2,4-dinitro-1-fluorobenzene. We also determined whether glutathione repletion with N-acetyl cysteine could influence the decline of the DTH response in aged mice.
Results
Glutathione depletion in bone marrow–derived DCs interfered in their ability to mount a DTH response on adoptive transfer into recipient mice. Glutathione depletion interfered in IL-12 production and costimulatory receptor expression in DCs, leading to decreased IFN-γ production in the skin of recipient mice. Systemic diethyl maleate treatment exerted similar effects on the DTH response and IFN-γ production, whereas N-acetyl cysteine administration reversed the decline of the DTH response in aged animals.
Begin_電腦自動翻譯的內容_Y2020m05d04h03m57Rn7867_
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
結果
骨髓來源的DC中的穀胱甘肽耗竭會干擾它們在過繼轉移到受體小鼠中時引起DTH反應的能力。穀胱甘肽耗竭會干擾DC中IL-12的產生和共刺激受體的表達，從而導致受體小鼠皮膚中IFN-γ的產生減少。全身性馬來酸二乙酯治療對DTH反應和IFN-γ產生具有相似的作用，而N-乙酰半胱胺酸的給藥可以逆轉衰老動物DTH反應的下降。
End_電腦自動翻譯的內容_Y2020m05d04h03m57Rn7867_
Conclusion
Glutathione depletion downregulates TH1 immunity through a perturbation of DC maturation and IL-12 production.
Clinical implications
These data show that the induction of oxidative stress in the immune system, under disease conditions and aging, interferes in TH1 immunity.
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
結果
骨髓來源的DC中的穀胱甘肽耗竭會干擾它們在過繼轉移到受體小鼠中時引起DTH反應的能力。穀胱甘肽耗竭會干擾DC中IL-12的產生和共刺激受體的表達，從而導致受體小鼠皮膚中IFN-γ的產生減少。全身性馬來酸二乙酯治療對DTH反應和IFN-γ產生具有相似的作用，而N-乙酰半胱胺酸的給藥可以逆轉衰老動物DTH反應的下降。
End_電腦自動翻譯的內容_Y2020m05d04h03m57Rn7867_
Conclusion
Glutathione depletion downregulates TH1 immunity through a perturbation of DC maturation and IL-12 production.
Clinical implications
These data show that the induction of oxidative stress in the immune system, under disease conditions and aging, interferes in TH1 immunity.
Begin_電腦自動翻譯的內容_Y2020m05d04h03m57Rn0875_
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
結論
穀胱甘肽耗竭通過乾擾DC成熟和IL-12產生而下調TH1免疫力。
臨床的意義
這些數據表明，在疾病條件和衰老過程中，免疫系統中氧化壓力的誘導會干擾TH1免疫。
End_電腦自動翻譯的內容_Y2020m05d04h03m57Rn0875_
Key words
Dendritic cells
TH1
glutathione
delayed-type hypersensitivity
skin dermatitis
aging
antigen-presenting cells
redox
(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
結論
穀胱甘肽耗竭通過乾擾DC成熟和IL-12產生而下調TH1免疫力。
臨床的意義
這些數據表明，在疾病條件和衰老過程中，免疫系統中氧化壓力的誘導會干擾TH1免疫。
End_電腦自動翻譯的內容_Y2020m05d04h03m57Rn0875_
Key words
Dendritic cells
TH1
glutathione
delayed-type hypersensitivity
skin dermatitis
aging
antigen-presenting cells
redox
Abbreviations used:
APC (Antigen-presenting cell), BM-DC (Bone marrow–derived dendritic cell), CON (Vehicle-treated control), DC (Dendritic cell), DEM (Diethyl maleate), DEP (Diesel exhaust particle), DNBS (2,4-Dinitrobenzene sulfonic acid), DNFB (2,4-Dinitro-1-fluorobenzene), DTH (Delayed-type hypersensitivity), FITC (Fluorescein isothiocyanate), MBB (Monobromobimane), MLR (Mixed-leukocyte reaction), NAC (N-acetyl cysteine), OXA (Oxazolone), PE (Phycoerythrin), ROS (Reactive oxygen species), Treg (Regulatory T)
APC (Antigen-presenting cell), BM-DC (Bone marrow–derived dendritic cell), CON (Vehicle-treated control), DC (Dendritic cell), DEM (Diethyl maleate), DEP (Diesel exhaust particle), DNBS (2,4-Dinitrobenzene sulfonic acid), DNFB (2,4-Dinitro-1-fluorobenzene), DTH (Delayed-type hypersensitivity), FITC (Fluorescein isothiocyanate), MBB (Monobromobimane), MLR (Mixed-leukocyte reaction), NAC (N-acetyl cysteine), OXA (Oxazolone), PE (Phycoerythrin), ROS (Reactive oxygen species), Treg (Regulatory T)
Oxidative stress is a state of redox
disequilibrium that is defined as a depletion of intracellular glutathione and
an accumulation of glutathione disulfide. A decline
of the cellular glutathione/glutathione disulfide ratio initiates a series of
biological responses that are relevant to normal physiology as well as the
pathophysiology of disease. According to the hierarchical oxidative stress hypothesis, low levels of oxidative stress
initiate cellular antioxidant responses through nuclear factor-erythroid
2 (NF-E2)–related factor 2 (Nrf2)-mediated phase II enzyme (eg, catalase and
superoxide dismutase) expression.1 At higher levels of oxidative stress, activation
of the mitogen-activated protein kinase and NF-κB signaling cascades culminate
in proinflammatory effects, whereas
at the highest level of oxidative stress, interference in mitochondrial
function leads to ATP depletion and programmed cell death.1 This dynamic interplay between protective
and injurious oxidative stress responses could modulate the immune
response in asthma, AIDS, diabetes mellitus, contact dermatitis, and
cancer.2, 3, 4, 5, 6 Moreover, several of the biological effects of aging have been
ascribed to altered redox equilibrium and generation of excessive reactive
oxygen species (ROSs).6
Oxidative stress is of key
importance in the effector as well as the induction phases of the immune
response.5, 6, 7 It is well known that immune activation generates inflammatory states in
which ROS production by immune cells contributes to protective as well as
tissue damaging effects. Less appreciated is that ROS and oxidative stress also regulate the
induction of the immune response by controlling signal transduction pathways in
antigen-presenting cells (APCs) and lymphocytes.8 ROSs not only regulate T-cell
activation but also interfere in the polarity of the immune response as
evidenced by the finding that oxidative stress favors TH2 skewing of the immune
response while suppressing TH1 differentiation.8, 9 Accordingly, glutathione depletion in vivo results in lowered TH1 but
increased TH2 responses, whereas glutathione repletion has the opposite effect.8
The elucidation of the mechanisms by which oxidative stress changes APC
function is of key importance in studying the pathophysiology of disease as
well as understanding immune senescence.8,
9, 10
Although under disease conditions it is difficult to regulate the level of oxidative stress independent from pathological events, it is experimentally possible to obtain glutathione depletion with the thiol-alkylating agent, diethyl maleate (DEM).11 We used this agent to treat dendritic cells (DCs) ex vivo as well as deplete glutathione levels in mice to study the effects of oxidative stress on the delayed-type hypersensitivity (DTH) response and cytokine profiles in the skin. Adjustable levels of oxidative stress could be achieved in DCs as well as the lymph nodes and spleens of DEM-treated animals. Glutathione depletion interferes in the expression of costimulatory receptors and IL-12 production in bone marrow–derived DCs (BM-DCs), making these cells less capable of supporting a DTH response and TH1 immunity after adoptive transfer in vivo. DEM also interfered in DTH responses in intact animals, whereas the glutathione precursor, N-acetyl cysteine (NAC), reversed the decline in the DTH response in aged mice.
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Although under disease conditions it is difficult to regulate the level of oxidative stress independent from pathological events, it is experimentally possible to obtain glutathione depletion with the thiol-alkylating agent, diethyl maleate (DEM).11 We used this agent to treat dendritic cells (DCs) ex vivo as well as deplete glutathione levels in mice to study the effects of oxidative stress on the delayed-type hypersensitivity (DTH) response and cytokine profiles in the skin. Adjustable levels of oxidative stress could be achieved in DCs as well as the lymph nodes and spleens of DEM-treated animals. Glutathione depletion interferes in the expression of costimulatory receptors and IL-12 production in bone marrow–derived DCs (BM-DCs), making these cells less capable of supporting a DTH response and TH1 immunity after adoptive transfer in vivo. DEM also interfered in DTH responses in intact animals, whereas the glutathione precursor, N-acetyl cysteine (NAC), reversed the decline in the DTH response in aged mice.
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