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Former Division Chief Blood and Marrow Transplant
President Elect American Society of…
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Happy to share this piece in the next issue of ASH Clinical News. I look forward to seeing you in Orlando for the ASH meeting!
Happy to share this piece in the next issue of ASH Clinical News. I look forward to seeing you in Orlando for the ASH meeting!
Shared by Robert Negrin, MD
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Protecting research takes all of us. Last week, over the course of five hours, I had the privilege of speaking with more than 20 TV and radio…
Protecting research takes all of us. Last week, over the course of five hours, I had the privilege of speaking with more than 20 TV and radio…
Shared by Robert Negrin, MD
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Critical time for NIH funding in the next few weeks. Keep writing your legislators. Go to #Fight4Hematology to find an easy way to send letters…
Critical time for NIH funding in the next few weeks. Keep writing your legislators. Go to #Fight4Hematology to find an easy way to send letters…
Posted by Robert Negrin, MD
Experience
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Harvard Medical School
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IL-17 Gene Ablation Does Not Impact Treg-Mediated Suppression of Graft-Versus-Host Disease Following Bone Marrow Transplantation.
Biology of Blood and Marrow Transplantation
Regulatory T cell immunotherapy is a promising strategy for the treatment of graft rejection responses and autoimmune disorders. Our and other laboratories have shown that the transfer of highly purified CD4+CD25+Foxp3+ natural regulatory T cells (Treg) can prevent lethal graft-versus host disease (GVHD) following allogeneic hematopoietic cell transplantation across both major and minor histocompatibility barriers. However, recent evidence suggest that the Treg suppressive phenotype can become…
Regulatory T cell immunotherapy is a promising strategy for the treatment of graft rejection responses and autoimmune disorders. Our and other laboratories have shown that the transfer of highly purified CD4+CD25+Foxp3+ natural regulatory T cells (Treg) can prevent lethal graft-versus host disease (GVHD) following allogeneic hematopoietic cell transplantation across both major and minor histocompatibility barriers. However, recent evidence suggest that the Treg suppressive phenotype can become unstable, a phenomenon that can culminate in Treg conversion into IL-17-producing cells. We hypothesized that the intense proinflammatory signals released during an ongoing alloreaction might redirect a fraction of the transferred Treg to the Th17 cell fate, thereby losing immunosuppressive potential. We, therefore, sought to evaluate the impact of Il17 gene ablation on Treg stability and immunosuppressive capacity in a major MHC mismatch model. We show that while Il17 gene ablation results in a mildly enhanced Treg immunosuppressive ability in vitro, such improvement is not observed when IL-17-deficient Treg are used for GVHD suppression in vivo. Similarly, when we selectively blocked IL-1 signaling in Treg, that was shown to be necessary for Th17 conversion, we did not detect any improvement on Treg-mediated GVHD suppressive ability in vivo. Furthermore, upon ex vivo re-isolation of transferred wild type Treg, we detected little or no Treg-mediated IL-17 production upon GVHD induction. Our results indicate that blocking Th17 conversion does not affect the GVHD suppressive ability of highly purified natural Tregin vivo, suggesting that IL-17 targeting is not a valuable strategy to improve Treg immunotherapy following HCT.
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Sayna Norouzi MD
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Luca Saba
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