CD47-dependent regulation of H₂S biosynthesis and signaling in T cells.

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