Burgos, D. | Search bioRxiv

bioRxiv2025

Curing autoimmune diabetes with islet and hematopoietic cell transplantation after CD117 antibody-based conditioning

Mixed hematopoietic chimerism after allogeneic hematopoietic cell transplantation (HCT) promotes tolerance of transplanted donor-matched solid organs, corrects autoimmunity, and could transform therapeutic strategies for autoimmune type 1 diabetes (T1D). However, development of non-toxic bone marrow conditioning protocols is needed to expand clinical use. We developed a chemotherapy-free, non-myeloablative (NMA) conditioning regimen that achieves mixed chimerism and allograft tolerance across MHC barriers in NOD mice. We obtained durable mixed hematopoietic chimerism in prediabetic NOD mice using anti-c-Kit monoclonal antibody, T-cell depleting antibodies, JAK1/2 inhibition, and low-dose total body irradiation prior to transplantation of MHC-mismatched B6 hematopoietic cells, preventing diabetes in 100% of chimeric NOD:B6 mice. In overtly diabetic NOD mice, NMA conditioning followed by combined B6 HCT and islet transplantation durably corrected diabetes in 100% of chimeric mice without chronic immunosuppression or graft-versus-host disease (GVHD). Chimeric mice remained immunocompetent, as assessed by blood count recovery and rejection of 3rd party allogeneic islets. Adoptive transfer studies and analysis of autoreactive T cells confirmed correction of autoimmunity. Analysis of chimeric NOD mice revealed central thymic deletion and peripheral tolerance mechanisms. Thus, with NMA conditioning and cell transplantation, we achieved durable hematopoietic chimerism without GVHD, promoted islet allograft tolerance, and reversed established T1D. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/673576v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@23fcdorg.highwire.dtl.DTLVardef@1aac97borg.highwire.dtl.DTLVardef@191e06forg.highwire.dtl.DTLVardef@25be2b_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Detection of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in New York City

Highly pathogenic avian influenza viruses of the H5N1 clade 2.3.4.4b arrived in North America in the winter of 2021/2022. These viruses have spread across the Americas causing morbidity and mortality in both wild and domestic birds as well as some mammalian species, including cattle. Many surveillance programs in wildlife as well as commercial poultry operations have detected these viruses. Here we conducted surveillance of avian species in the urban environment in New York City. We detected highly pathogenic H5N1 viruses in six samples from four different bird species and performed full genome sequencing. Sequence analysis showed the presence of multiple different genotypes. Our work highlights that the interface between animals and humans that may give rise to zoonotic infections or even pandemics is not limited to rural environments and commercial poultry operations but extends into the heart of our urban centers. ImportanceWhile surveillance for avian influenza viruses is often focused on migratory routes and their associated stop-over locations, or commercial poultry operations, many bird species - including migratory birds - frequent or live in urban green spaces and wetlands. This brings them into contact with a highly dense population of humans and pets providing an extensive urban animal-human interface in which the general public may have little awareness of circulating infectious diseases. This study focuses on virus surveillance at this interface, combined with culturally responsive science education and community outreach.

microbiology↗