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CD47-dependent regulation of H₂S biosynthesis and signaling in T cells.
Methods Enzymol. 2015; 555:145-68.ME

Abstract

Pharmacological concentrations of H2S donors inhibit some T cell functions by inhibiting mitochondrial function, but evidence is also emerging that H2S at physiological concentrations produced via chemical sources and endogenously is a positive physiological mediator of T cell function. Expression of the H2S biosynthetic enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) is induced in response to T cell receptor signaling. Inhibiting the induction of these enzymes limits T cell activation and proliferation, which can be overcome by exposure to exogenous H2S at submicromolar concentrations. Exogenous H2S at physiological concentrations increases the ability of T cells to form an immunological synapse by altering cytoskeletal actin dynamics and increasing the reorientation of the microtubule-organizing center. Downstream, H2S enhances T cell receptor-dependent induction of CD69, CD25, and Interleukin-2 (IL-2) gene expression. The T cell stimulatory activity of H2S is enhanced under hypoxic conditions that limit its oxidative metabolism by mitochondrial and nonenzymatic processes. Studies of the receptor CD47 have revealed the first endogenous inhibitory signaling pathway that regulates H2S signaling in T cells. Binding of the secreted protein thrombospondin-1 to CD47 elicits signals that block the stimulatory activity of exogenous H2S on T cell activation and limit the induction of CSE and CBS gene expression. CD47 signaling thereby inhibits T cell receptor-mediated T cell activation.

Authors+Show Affiliations

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: droberts@helix.nih.gov.

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

25747479

Citation

Kaur, Sukhbir, et al. "CD47-dependent Regulation of H₂S Biosynthesis and Signaling in T Cells." Methods in Enzymology, vol. 555, 2015, pp. 145-68.
Kaur S, Schwartz AL, Miller TW, et al. CD47-dependent regulation of H₂S biosynthesis and signaling in T cells. Methods Enzymol. 2015;555:145-68.
Kaur, S., Schwartz, A. L., Miller, T. W., & Roberts, D. D. (2015). CD47-dependent regulation of H₂S biosynthesis and signaling in T cells. Methods in Enzymology, 555, 145-68. https://doi.org/10.1016/bs.mie.2014.11.023
Kaur S, et al. CD47-dependent Regulation of H₂S Biosynthesis and Signaling in T Cells. Methods Enzymol. 2015;555:145-68. PubMed PMID: 25747479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD47-dependent regulation of H₂S biosynthesis and signaling in T cells. AU - Kaur,Sukhbir, AU - Schwartz,Anthony L, AU - Miller,Thomas W, AU - Roberts,David D, Y1 - 2015/01/08/ PY - 2015/3/10/entrez PY - 2015/3/10/pubmed PY - 2015/12/15/medline KW - CD47 KW - Cystathionine β-synthase KW - Cystathionine γ-lyase KW - Hydrogen sulfide KW - Inflammation KW - T-cell activation KW - T-cell receptor KW - Thrombospondin-1 SP - 145 EP - 68 JF - Methods in enzymology JO - Methods Enzymol VL - 555 N2 - Pharmacological concentrations of H2S donors inhibit some T cell functions by inhibiting mitochondrial function, but evidence is also emerging that H2S at physiological concentrations produced via chemical sources and endogenously is a positive physiological mediator of T cell function. Expression of the H2S biosynthetic enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) is induced in response to T cell receptor signaling. Inhibiting the induction of these enzymes limits T cell activation and proliferation, which can be overcome by exposure to exogenous H2S at submicromolar concentrations. Exogenous H2S at physiological concentrations increases the ability of T cells to form an immunological synapse by altering cytoskeletal actin dynamics and increasing the reorientation of the microtubule-organizing center. Downstream, H2S enhances T cell receptor-dependent induction of CD69, CD25, and Interleukin-2 (IL-2) gene expression. The T cell stimulatory activity of H2S is enhanced under hypoxic conditions that limit its oxidative metabolism by mitochondrial and nonenzymatic processes. Studies of the receptor CD47 have revealed the first endogenous inhibitory signaling pathway that regulates H2S signaling in T cells. Binding of the secreted protein thrombospondin-1 to CD47 elicits signals that block the stimulatory activity of exogenous H2S on T cell activation and limit the induction of CSE and CBS gene expression. CD47 signaling thereby inhibits T cell receptor-mediated T cell activation. SN - 1557-7988 UR - https://www.unboundmedicine.com/medline/citation/25747479/CD47_dependent_regulation_of_H₂S_biosynthesis_and_signaling_in_T_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0076-6879(14)00088-3 DB - PRIME DP - Unbound Medicine ER -