Innate allorecognition induces HSP70 in monocytes contributing to renal allograft rejection
- 1Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
- 2Division of Transplant Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
- 3Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract
After encountering allogeneic nonself, monocytes differentiate to DCs, which in turn activate the adaptive immune system that drives transplant rejection. The downstream mechanisms of allorecognition are largely unknown. We analyzed scRNA-seq data sets to identify transcriptional changes in monocytes occurring after allostimulation. Hspa1a, which encodes HSP70, was upregulated in monocytes after allostimulation in contrast to syngeneic controls in mice lacking T, B, and NK cells. Similar findings were seen in scRNA-seq data derived from kidney biopsies of rejecting transplant patients. To validate the role of HSP70 in innate allorecognition and transplantation, we performed allogeneic bone marrow plug and kidney transplantation into WT, Hspa1a/Hspa1b–/–, and DSG-treated (HSP70 inhibitor) B6 mice and examined the graft immune infiltrate. Histology, T cell infiltration, and survival were assessed in kidney transplanted mice. In both models, DSG-treated or HSP70-KO recipients displayed significantly reduced infiltration by monocyte-derived DCs (mo-DC). Chronic rejection of Balb/c kidney grafts in WT B6 recipients was attenuated in DSG-treated and HSP70-KO recipients as indicated by a reduction in Banff score. Further experiments demonstrated that in vitro allostimulated immature HSP70-KO BMDC showed less maturation compared with WT BMDC. Targeting HSP70 in innate immune cells offers a novel approach to reduce chronic kidney graft rejection.
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BibTeX
@article{gui2026innate,
title = {{Innate allorecognition induces HSP70 in monocytes contributing to renal allograft rejection}},
author = {Zeping Gui and Neda Feizi and Berkay Demirors and Canxiang Lin and Hehua Dai and Mouhamad Al Moussawy and Andrew Friday and Steven M. Sanders and Latha Halesha and Amanda L. Williams and Faruk Sacirbegovic and Parmjeet S. Randhawa and Khodor I. Abou-Daya and Martin H. Oberbarnscheidt},
journal = {JCI Insight},
year = {2026},
month = oct,
doi = {10.1172/jci.insight.197348},
url = {https://doi.org/10.1172/jci.insight.197348},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Innate allorecognition induces HSP70 in monocytes contributing to renal allograft rejection
AU - Zeping Gui
AU - Neda Feizi
AU - Berkay Demirors
AU - Canxiang Lin
AU - Hehua Dai
AU - Mouhamad Al Moussawy
AU - Andrew Friday
AU - Steven M. Sanders
AU - Latha Halesha
AU - Amanda L. Williams
AU - Faruk Sacirbegovic
AU - Parmjeet S. Randhawa
AU - Khodor I. Abou-Daya
AU - Martin H. Oberbarnscheidt
PY - 2026
DA - 2026/10/08
JO - JCI Insight
DO - 10.1172/jci.insight.197348
UR - https://doi.org/10.1172/jci.insight.197348
AB - After encountering allogeneic nonself, monocytes differentiate to DCs, which in turn activate the adaptive immune system that drives transplant rejection. The downstream mechanisms of allorecognition are largely unknown. We analyzed scRNA-seq data sets to identify transcriptional changes in monocytes occurring after allostimulation. Hspa1a, which encodes HSP70, was upregulated in monocytes after allostimulation in contrast to syngeneic controls in mice lacking T, B, and NK cells. Similar findings were seen in scRNA-seq data derived from kidney biopsies of rejecting transplant patients. To validate the role of HSP70 in innate allorecognition and transplantation, we performed allogeneic bone marrow plug and kidney transplantation into WT, Hspa1a/Hspa1b–/–, and DSG-treated (HSP70 inhibitor) B6 mice and examined the graft immune infiltrate. Histology, T cell infiltration, and survival were assessed in kidney transplanted mice. In both models, DSG-treated or HSP70-KO recipients displayed significantly reduced infiltration by monocyte-derived DCs (mo-DC). Chronic rejection of Balb/c kidney grafts in WT B6 recipients was attenuated in DSG-treated and HSP70-KO recipients as indicated by a reduction in Banff score. Further experiments demonstrated that in vitro allostimulated immature HSP70-KO BMDC showed less maturation compared with WT BMDC. Targeting HSP70 in innate immune cells offers a novel approach to reduce chronic kidney graft rejection.
SN - 2379-3708
ER -