NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs

Wen, Zhenke; Shimojima, Yasuhiro; Shirai, Toshikazu; Li, Yinyin; Ju, Jihang; Yang, Zhen; Tian, Lu; Goronzy, Jörg J.; Weyand, Cornelia M.

doi:10.1172/jci84181

Cited by 116 publications

(125 citation statements)

References 69 publications

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“…ROS produced by monocytes can also inhibit interacting cells, for example, NK cells or classical αβ T cells during antigen presentation 27 28. ROS can be released within the immunological synapse or by transfer of exosomes containing NOX2 to CD4 T cells 29. These findings all point to the crucial role that ROS play in controlling the immune response and preventing excessive activation of immune effector cells, such as T cells and NK cells.…”

Section: Discussionmentioning

confidence: 91%

A single nucleotide polymorphism in theNCF1gene leading to reduced oxidative burst is associated with systemic lupus erythematosus

et al. 2017

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Section: Discussionmentioning

confidence: 91%

A single nucleotide polymorphism in theNCF1gene leading to reduced oxidative burst is associated with systemic lupus erythematosus

et al. 2017

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“…The co-occurrence of weakened adaptive immunity with a bias toward nonspecific tissue inflammation is often captured in the term "inflammaging." Mechanisms fostering inflammatory disease in the old include the loss of immunoinhibitory capacity, specifically the deterioration of regulatory T-cell (Treg) function (50)(51)(52). Immune aging is a risk factor for and amplifies many of the pathologies associated with the aging process.…”

Section: Resultsmentioning

confidence: 99%

Aging of the Immune System. Mechanisms and Therapeutic Targets

2016

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Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease. Immune system aging functions as an accelerator for other age-related pathologies. It occurs prematurely in some clinical conditions, most prominently in patients with the autoimmune syndrome rheumatoid arthritis (RA); and such patients serve as an informative model system to study molecular mechanisms of immune aging. T cells from patients with RA are prone to differentiate into proinflammatory effector cells, sustaining chronic-persistent inflammatory lesions in the joints and many other organ systems. RA T cells have several hallmarks of cellular aging; most importantly, they accumulate damaged DNA. Because of deficiency of the DNA repair kinase ataxia telangiectasia mutated, RA T cells carry a higher burden of DNA double-strand breaks, triggering cell-indigenous stress signals that shift the cell's survival potential and differentiation pattern. Immune aging in RA T cells is also associated with metabolic reprogramming; specifically, with reduced glycolytic flux and diminished ATP production. Chronic energy stress affects the longevity and the functional differentiation of older T cells. Altered metabolic patterns provide opportunities to therapeutically target the immune aging process through metabolic interference.

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“…Data on Treg function in GCA are sparse, but a recent study has provided evidence that GCA patients are lacking a potent immunoregulatory CD8 Treg population (26), compatible with PD-L1 deficiency shaping a vasculitogenic T-cell repertoire. When analyzing disease-relevant effector T cells, PD-1 appeared to be expressed on multiple T-cell lineages (Fig.…”

Section: Discussionmentioning

confidence: 99%

Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis

Zhang

Watanabe

Berry

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Giant cell arteritis (GCA) causes autoimmune inflammation of the aorta and its large branches, resulting in aortic arch syndrome, blindness, and stroke. CD4+ T cells and macrophages form organized granulomatous lesions in the walls of affected arteries, destroy the tunica media, and induce ischemic organ damage through rapid intimal hyperplasia and luminal occlusion. Pathogenic mechanisms remain insufficiently understood; specifically, it is unknown whether the unopposed activation of the immune system is because of deficiency of immunoinhibitory checkpoints. Transcriptome analysis of GCA-affected temporal arteries revealed low expression of the coinhibitory ligand programmed death ligand-1 (PD-L1) concurrent with enrichment of the programmed death-1 (PD-1) receptor. Tissue-residing and ex vivo-generated dendritic cells (DC) from GCA patients were PD-L1 lo

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NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs

Cited by 116 publications

References 69 publications

A single nucleotide polymorphism in theNCF1gene leading to reduced oxidative burst is associated with systemic lupus erythematosus

A single nucleotide polymorphism in theNCF1gene leading to reduced oxidative burst is associated with systemic lupus erythematosus

Aging of the Immune System. Mechanisms and Therapeutic Targets

Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis

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