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10.1681/ASN.2013090945

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C4147979!4147979!24676641
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suck abstract from ncbi


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pmid24676641      J+Am+Soc+Nephrol 2014 ; 25 (9): 2003-15
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  • Immunosuppressive Effects of Erythropoietin on Human Alloreactive T Cells #MMPMID24676641
  • Cravedi P; Manrique J; Hanlon KE; Reid-Adam J; Brody J; Prathuangsuk P; Mehrotra A; Heeger PS
  • J Am Soc Nephrol 2014[Sep]; 25 (9): 2003-15 PMID24676641show ga
  • Correction of anemia with erythropoietin (EPO) is associated with improved kidney transplant outcomes. Emerging evidence, predominantly from animal models, indicates that these observations may be erythropoiesis-independent and that EPO exhibits immunosuppressive properties. We examined the effects of EPO on human T-cell alloimmunity by first documenting that CD4+ and CD8+ T cells express EPO receptor (EPO-R) on their surfaces. In mixed lymphocyte reactions, EPO induced a dose-dependent decrease in allogeneic CD4+ T-cell proliferation (EPO 1000 U/ml: 44.6%±22.9% of vehicle, P<0.05; 2000 U/ml: 11.1%±4% of vehicle, P<0.001) without inducing cell death. The effects required signals transmitted directly through the EPO-R expressed on T cells, resulting in diminished Th1 differentiation without effects on regulatory T-cell induction. Mechanistic studies revealed that EPO prevented IL-2?induced proliferation by uncoupling IL-2 receptor signaling, inhibiting phosphorylation of the intracellular intermediaries AKT and extracellular signal-regulated kinase that are known to mediate T-cell expansion. EPO treatment reduced expansion of human naïve CD4+ T cells after adoptive transfer into NOD scid?cnull mouse recipients, verifying the effects in vivo. Although activated T cells expressed CD131, an alternative EPO receptor, addition of a specific CD131 agonist peptide, ARA290, did not alter T-cell proliferation or cytokine production. Our findings link EPO-R signaling on T cells to inhibition of T-cell immunity, providing one mechanism that could explain the observed protective effects of EPO in kidney transplant recipients.
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