Publications by authors named "Michael J Ehrhardt"

Article Synopsis
  • Multisystem inflammatory syndrome in children (MIS-C) is a serious condition linked to COVID-19, causing inflammation and affecting multiple organs.
  • Research indicates that while antibodies are produced, there are issues with cell-mediated immune responses, particularly with natural killer (NK) cells, which show reduced functionality.
  • Possible treatments, like using CD16 cellular engagers, may improve NK cell function and help address the immune system's dysregulation associated with MIS-C.
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Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multi-organ involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong antibody production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 weeks after infection.

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Tissue engineering using decellularized whole lungs as matrix scaffolds began as a promise for creating autologous transplantable lungs for patients with end-stage lung disease and can also be used to study strategies for lung regeneration. Vascularization remains a critical component for all solid organ bioengineering, yet there has been limited success in generating functional re-endothelialization of most pulmonary vascular segments. We evaluated recellularization of the blood vessel conduits of acellular mouse scaffolds with highly proliferating, rat pulmonary microvascular endothelial progenitor cells (RMEPCs), pulmonary arterial endothelial cells (PAECs) or microvascular endothelial cells (MVECs).

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Rett syndrome (RTT) is a severe neurodevelopmental disorder resulting from mutations of the MECP2 gene. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal stress responses have been observed in animal models of RTT, but little is known about HPA axis function among individuals with RTT. Diurnal salivary cortisol patterns from 30 females with RTT were examined in relation to mutation type, medication use, and features of the RTT behavioral phenotype.

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Background: Immune dysregulation may play a role in the development of Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations of the MECP2 gene. Abnormal cytokine concentrations have been documented in the serum of individuals with RTT. Measurement of salivary cytokines has been investigated as a potential alternative approach to measurement in blood and serum, but it is unclear whether salivary cytokine concentrations can provide valid information about systemic immune function in neurodevelopmental disorders.

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Rationale: Obliterative bronchiolitis (OB) is a significant cause of morbidity and mortality after lung transplant and hematopoietic cell transplant. Mesenchymal stromal cells (MSCs) have been shown to possess immunomodulatory properties in chronic inflammatory disease.

Objective: Administration of MSCs was evaluated for the ability to ameliorate OB in mice using our established allogeneic bone marrow transplant (BMT) model.

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Article Synopsis
  • CpG ODNs are synthetic oligodeoxynucleotides that mimic bacterial DNA, activating immune responses that can enhance the lethality of graft-versus-host disease (GVHD) through Toll-like receptor 9 (TLR9) without relying on specific cytokines like IL-12 or IL-6.
  • The studies reveal that CpG ODNs facilitate the rejection of allogeneic donor bone marrow by signaling through donor, rather than host, TLR9, highlighting the significant role of donor bone marrow antigen-presenting cells in this rejection process.
  • Findings indicate that the presence of certain immune cell types, such as myeloid cells, is crucial in modifying the host's rejection response, suggesting
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The immunomodulator FTY720 (FTY) has been shown to be beneficial in experimental models of organ transplantation and autoimmunity. We show that FTY significantly inhibited but did not prevent graft-versus-host disease (GVHD) in lethally irradiated or nonirradiated allogeneic recipients. Although most studies implicate prevention of lymphocyte egress from lymphoid organs as the primary mechanism of action, our data indicate that FTY effects on the host are more likely to be responsible for GVHD inhibition.

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Multiply-transfused individuals are at higher risk for BM rejection. We show that whereas allosensitization resulted in the priming of both cellular and humoral immunity, preformed antibody was the major barrier to engraftment. The generation of cross-reactive alloantibody led to rejection of BM of a different MHC-disparate strain.

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The immunosuppressive drugs, cyclosporine A (CsA), tacrolimus, or sirolimus, were analyzed as single agents and in combination with anti-CD40L monoclonal antibody (mAb) for their effects on alloengraftment in mice conditioned with minimal total body irradiation (TBI). Whereas anti-CD40L mAb facilitated chimerism, neither sirolimus nor CsA resulted in substantial alloengraftment. However, sirolimus was synergistic with anti-CD40L mAb for inducing donor chimerism.

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