Session Name: Innate Immunity; Chemokines, Cytokines, Complement
Session Date & Time: None. Available on demand.
*Purpose: Kidney-resident macrophages play important roles in maintaining normal kidney function and promoting prompt repair following kidney injuries. Nevertheless, their fate and role in kidney transplantation remain unknown.
*Methods: Donor kidneys from BALB/c mice (CD45.2) were transplanted into bilaterally nephrectomized C57BL/6 (B6; CD45.1) recipients. Untreated transplant recipients were sacrificed at various time points to track donor kidney-resident macrophages. To investigate the role of donor kidney-resident macrophage, these cells were depleted by treating BALB/c donors with clodronate-liposomes (200 μl/mouse for a week) prior to the transplantation into B6 recipients (Clodro Group). A Control Group of B6 recipients received kidney allografts from BABL/c donors treated with control liposomes without clodronate. Post-transplant intragraft inflammation and cellular infiltration were determined using qPCR and FACS.
*Results: In naïve untransplanted donor kidneys, resident macrophages were identified as F4/80HICD11cINTMHCIIHICCR2– cells, constituting ~25% of total CD11b+ myeloid cells. Post-transplantation, the majority of these cells of donor-origin were eliminated by day7, and were undetectable by day15 in rejecting kidney allografts from untreated recipients. FACS analysis of graft-infiltrating recipient CD45.1+ monocytes/macrophages from Control Group on day7 post-transplant revealed elevated expression of MHC II and co-stimulatory CD86. These cells also expressed elevated level of inflammatory cytokine TNFα measured by intracellular cytokine staining. qPCR analysis of allografts also demonstrated elevated levels of Il17a and Ccl8. Interestingly, all of these immune parameters were significantly downregulated in Clodro Group. In addition, the number of graft-infiltrating CD8 T cells also reduced significantly in Clodro Group in comparison to Control Group.
*Conclusions: Our data demonstrate that donor kidney-resident macrophages may cause acute kidney allograft injury post-transplantation by promoting inflammation and CD8 T cell-infiltration. It is well recognized that acute kidney allograft-injury has detrimental effects on long-term transplant outcome. Thus, as a proof of concept our data suggest that targeting donor kidney-resident macrophages, probably during preservation time, may improve transplant outcomes.
To cite this abstract in AMA style:Dangi A, Yu S, Husain I, Geesala R, Luo X. Donor Kidney-Resident Macrophages Promote Allograft Inflammation and CD8 T Cell Response Post-Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-kidney-resident-macrophages-promote-allograft-inflammation-and-cd8-t-cell-response-post-transplantation/. Accessed June 18, 2021.
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