دورية أكاديمية
Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants.
| العنوان: | Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants. |
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| المؤلفون: | Ashraf MI; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Mengwasser J; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany., Reutzel-Selke A; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Polenz D; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Führer K; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Lippert S; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Tang P; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Michaelis E; Department of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany., Catar R; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Healthy, Berlin, Germany., Pratschke J; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Witzel C; Department of Plastic Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Sauer IM; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Tullius SG; Division of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.; Einstein Berlin Institute of Health Visiting Fellow, Charité - Universitätsmedizin Berlin, Berlin, Germany., Kern B; Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Department of Plastic Surgery, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin Institute of Health (BIH) Biomedical Innovation Academy, Berlin Institute of Health (BIH) Charité Clinician Scientist Program, Berlin, Germany. |
| المصدر: | Frontiers in immunology [Front Immunol] 2024 May 10; Vol. 15, pp. 1395945. Date of Electronic Publication: 2024 May 10 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Dendritic Cells*/immunology , Skin Transplantation* , Hindlimb*/immunology , Hindlimb*/transplantation , Graft Rejection*/immunology , Graft Rejection*/prevention & control, Animals ; Mice ; Mice, Inbred C57BL ; Mice, Inbred BALB C ; Composite Tissue Allografts/immunology ; Vascularized Composite Allotransplantation/methods ; CD8-Positive T-Lymphocytes/immunology ; Male ; Tissue Donors ; Skin/immunology |
| مستخلص: | Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APCs), particularly dendritic cells (DCs), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DCs (cDCs) and APCs 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. Notably, the skin component exhibited heightened immunogenicity when compared to the entire VCA, evidenced by increased frequencies of pan (CD11b - CD11c + ), mature (CD11b - CD11c + MHCII + ) and active (CD11b - CD11c + CD40 + ) DCs and cDC2 subset (CD11b + CD11c + MHCII + ) in the lymphoid tissues and the blood of skin transplant recipients. While donor depletion of cDC and APC reduced frequencies, maturation and activation of DCs in all analyzed 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 APCs and cDCs mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Ashraf, Mengwasser, Reutzel-Selke, Polenz, Führer, Lippert, Tang, Michaelis, Catar, Pratschke, Witzel, Sauer, Tullius and Kern.) |
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| فهرسة مساهمة: | Keywords: Th17 immune response; acute cellular rejection; allograft immunogenicity; antigen presenting cells (APCs); conventional dendritic cells (cDCs); mouse models of skin and hind limb transplantation; vascularized composite-tissue allografts (VCA) |
| تواريخ الأحداث: | Date Created: 20240527 Date Completed: 20240527 Latest Revision: 20240528 |
| رمز التحديث: | 20240528 |
| مُعرف محوري في PubMed: | PMC11116604 |
| DOI: | 10.3389/fimmu.2024.1395945 |
| PMID: | 38799435 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2024.1395945 |