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DFG Walter-Benjamin grant for the investigation of sex as a biological variable in alloimmunity
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With a DFG Walter-Benjamin grant Dr. med. Friederike Martin will join the laboratory of Transplant Surgery Research at Harvard under the direction of Professor Stefan G. Tullius in Boston to investigate the role of biological sex for transplantation outcome.

Influences of donor and recipient sex on transplantation outcome have been described manifold, as well as an influence of sex hormones on the innate and adaptive immune response. So far, research, investigating the impact of sex hormones and different sex- and age-dependent sex-hormone levels on alloimmune response after solid organ transplantation is lacking. The aim of the project “Sex as a biological Variable in Alloimmunity” is, to delineate the impact of sex hormones and especially estrogens and age-dependent changes in estrogen-levels on alloimmune response after allogenic transplantation.  The project is based on the publication “Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion” published in the AJT in 2021 by the workgroup of Prof. Tullius.

Friederike, who already received the Sanofi Women in Transplantation fellowship grant for research in gender and sex in transplantation in 2021, will work as a Postdoc on this project in the Tullius Lab for an expected 2 years period, starting in January 2023.


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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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