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LTx – microRNA signatures in peripheral blood ?
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BIOMARKERS accepted our latest paper on „microRNA signatures in peripheral blood fail to detect acute cellular rejection after liver transplantation“ for publication. Authors are N. Raschzok, A. Reutzel-Selke, R. Schmuck, L. Tannus, M. Morgul, C. Dietel, A. Leder, B. Struecker, S. Lippert, H. Sallmon, M. Schmelzle, M. Bartels, S. Jonas, J. Pratschke, and I.M. Sauer.

We investigated whether microRNA signatures in whole blood samples are associated with acute cellular rejection (ACR) after liver transplantation. Blood samples were collected using Paxgene technology and analyzed by microarrays and qRT-PCR. microRNA signatures failed to distinguish between 19 patients with ACR and 16 controls. Let-7b-5p and let-7c were up-regulated in a subgroup of patients with ACR during the 6th and 7th postoperative day but failed in an independent validation of 20 patients. microRNA signatures in whole blood processed by Paxgene technology are not suited for detection of ACR after liver transplantation.
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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