Hydrogen Sulfide Is an Endogenous Potentiator of T Cell Activation

Miller, Thomas W.; Wang, Evelyn A.; Gould, Serge; Stein, Elizabeth; Kaur, Sukhbir; Lim, Li Hong Idris; Amarnath, Shoba; Fowler, Daniel H.; Roberts, D. A.

doi:10.1074/jbc.m111.307819

Cited by 124 publications

(98 citation statements)

References 67 publications

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“…4 Accordingly, CSE-deficient mice (CSE 2/2 ) develop hypertension, 3 analogous to mice lacking endothelial nitric oxide synthase 5 and CBS +/2 mice. 6 In addition, endogenously produced H 2 S is involved in cellular proliferation, 7 angiogenesis, 8 inflammation 9,10 and regulation of protein activity through S-sulfhydration. [11][12][13] Exogenous treatment with H 2 S can induce a reversible hypometabolic, hibernation-like state.…”

mentioning

confidence: 99%

Cystathionine γ-Lyase Protects against Renal Ischemia/Reperfusion by Modulating Oxidative Stress

Bos

Wang

Snijder³

et al. 2013

Journal of the American Society of Nephrology

172

147

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Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter with physiologic functions similar to nitric oxide and carbon monoxide. Exogenous treatment with H 2 S can induce a reversible hypometabolic state, which can protect organs from ischemia/reperfusion injury, but whether cystathionine g-lyase (CSE), which produces endogenous H 2 S, has similar protective effects is unknown. Here, human renal tissue revealed abundant expression of CSE, localized to glomeruli and the tubulointerstitium. Compared with wild-type mice, CSE knockout mice had markedly reduced renal production of H 2 S, and CSE deficiency associated with increased damage and mortality after renal ischemia/reperfusion injury. Treatment with exogenous H 2 S rescued CSE knockout mice from the injury and mortality associated with renal ischemia. In addition, overexpression of CSE in vitro reduced the amount of reactive oxygen species produced during stress. Last, the level of renal CSE mRNA at the time of organ procurement positively associated with GFR 14 days after transplantation. In summary, these results suggest that CSE protects against renal ischemia/reperfusion injury, likely by modulating oxidative stress through the production of H 2 S.

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mentioning

confidence: 99%

Cystathionine γ-Lyase Protects against Renal Ischemia/Reperfusion by Modulating Oxidative Stress

Bos

Wang

Snijder³

et al. 2013

Journal of the American Society of Nephrology

172

147

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“…Furthermore, activation increased the capacity of T cells to make H 2 S by increasing expression of cystathionine c-lyase (CSE) and cystathionine b-synthase (CBS). Disrupting this response by using siRNA to target these enzymes impaired T cell activation and proliferation, which could be rescued by the addition of 300 nM H 2 S. At physiological concentrations, H 2 S also induced formation of the immunological synapse by altering cytoskeletal actin dynamics in the microtubule organizing center during T cell activation (166).…”

Section: A Role Of H 2 S In T Cell Activationmentioning

confidence: 99%

“…Exposure of Jurkat T cells to 1-5 mM NaHS at pH 6.0-8.0 induced blebbing and apoptosis by activation of the Rho-Rock pathway and cleavage of caspase-3 and poly-ADP ribose polymerase (PARP) (107). In contrast, H 2 S at physiological concentrations (<10 lM) is a positive physiological enhancer of T cell function (166) (Fig. 7).…”

Section: A Role Of H 2 S In T Cell Activationmentioning

confidence: 99%

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

Roberts

Kaur

Isenberg

2017

Antioxidants & Redox Signaling

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Significance: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Critical Issues: Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Future Directions: Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

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“…H 2 S also enhances T-cell proliferation, suggesting that H 2 S represents a novel immunomodulatory molecule in T cells (Miller et al 2012; Fig. 2A).…”

Section: H 2 S Governs T-cell Homeostasismentioning

confidence: 99%

“…2B). H 2 S serves as a costimulator to govern T-cell activation, proliferation, and lineage determination (Miller et al 2012). It may be a novel therapeutic approach for inflammation and autoimmune disease treatment via targeting H 2 S metabolism.…”

Section: H 2 S Governs T-cell Homeostasismentioning

confidence: 99%

Hydrogen Sulfide Regulates Homeostasis of Mesenchymal Stem Cells and Regulatory T Cells

2016

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Hydrogen sulfide (H 2 S) has long been known as a toxic gas. However, recently accumulated evidence suggests that H 2 S contributes to a variety of physiologic and pathologic processes. Endogenous H 2 S production is regulated by multiple enzymes that are differentially expressed in the cardiovascular, neuronal, immune, renal, respiratory, gastrointestinal, reproductive, liver, and endocrine systems. Alteration of H 2 S metabolism may affect multiple signaling pathways and tissue homeostasis. The growing number of diverse targets for which H 2 S serves as a gasotransmitter has been extensively reviewed elsewhere. In this review, the authors discuss current emerging evidence that H 2 S regulates mesenchymal stem cell and T-cell functions.

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Hydrogen Sulfide Is an Endogenous Potentiator of T Cell Activation

Cited by 124 publications

References 67 publications

Cystathionine γ-Lyase Protects against Renal Ischemia/Reperfusion by Modulating Oxidative Stress

Cystathionine γ-Lyase Protects against Renal Ischemia/Reperfusion by Modulating Oxidative Stress

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

Hydrogen Sulfide Regulates Homeostasis of Mesenchymal Stem Cells and Regulatory T Cells

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