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10.1172/jci.insight.91701 http://scihub22266oqcxt.onion/10.1172/jci.insight.91701 C5436544!5436544!28515365     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       JCI+Insight ä ; 2 (10): ä Nephropedia Template TP {{tp|p=28515365|t=ä. Ceramide synthesis regulates T cell activity and GVHD development |pdf=|usr=}}{{28515365}} gab.com Text Ceramide synthesis regulates T cell activity and GVHD development JO: JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=28515365 #FOAvip Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined. In the current study, we specifically characterized the role of ceramide synthase 6 (CerS6) after allo-HCT using genetic and pharmacologic approaches. We found that CerS6 was required for optimal T cell activation, proliferation, and cytokine production in response to alloantigen and for subsequent induction of GVHD. However, CerS6 was partially dispensable for the T cell?mediated antileukemia effect. At the molecular level, CerS6 was required for efficient TCR signal transduction, including tyrosine phosphorylation, ZAP-70 activation, and PKC?/TCR colocalization. Impaired generation of C16-ceramide was responsible for diminished allogeneic T cell responses. Furthermore, targeting CerS6 using a specific inhibitor significantly reduced T cell activation in mouse and human T cells in vitro. Our study provides a rationale for targeting CerS6 to control GVHD, which would enhance the efficacy of allo-HCT as an immunotherapy for hematologic malignancies in the clinic. Twit Text FOAVip Ceramide synthesis regulates T cell activity and GVHD development ????JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=28515365 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28515365 #FOAvip English Wikipedia <ref>{{Cite pmid|28515365}}</ref> Ceramide synthesis regulates T cell activity and GVHD development #MMPMID28515365 Sofi MH; Heinrichs J; Dany M; Nguyen H; Dai M; Bastian D; Schutt S; Wu Y; Daenthanasanmak A; Gencer S; Zivkovic A; Szulc Z; Stark H; Liu C; Chang YJ; Ogretmen B; Yu XZ JCI Insight ä[]; 2 (10): ä PMID28515365show ga Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined. In the current study, we specifically characterized the role of ceramide synthase 6 (CerS6) after allo-HCT using genetic and pharmacologic approaches. We found that CerS6 was required for optimal T cell activation, proliferation, and cytokine production in response to alloantigen and for subsequent induction of GVHD. However, CerS6 was partially dispensable for the T cell?mediated antileukemia effect. At the molecular level, CerS6 was required for efficient TCR signal transduction, including tyrosine phosphorylation, ZAP-70 activation, and PKC?/TCR colocalization. Impaired generation of C16-ceramide was responsible for diminished allogeneic T cell responses. Furthermore, targeting CerS6 using a specific inhibitor significantly reduced T cell activation in mouse and human T cells in vitro. Our study provides a rationale for targeting CerS6 to control GVHD, which would enhance the efficacy of allo-HCT as an immunotherapy for hematologic malignancies in the clinic. äCeramide synthesis regulates T cell activity and GVHD development (epmc).pdf DeepDyve Pubget Overpricing