Brent H. Koehn

Inflammasome-resistant IPSC-derived myeloid-derived suppressor cells ameliorate xenogeneic graft-versus-host disease

Lie Ma, Brent H. Koehn, Michael Zaiken, Keli L. Hippen et autres

ABSTRACT: Front-line pharmaceutical interventions for treating acute graft-versus-host disease (GVHD) are not uniformly effective and have toxic side effects. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with potent in vitro and in vivo immunosuppressive functions. Clinical translation …

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The role of VISTA engagement in limiting neutrophil-mediated inflammation

Elizabeth C. Nowak, Jiannan Li, Zachary T. Peters, Lindsay Mendyka et autres

A growing body of evidence suggests that the immune checkpoint inhibitory receptor VISTA plays a central role in the regulation of innate immunity in the settings of inflammatory diseases and cancer. Neutrophils are among the cells that have the highest membrane density …

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Immunoregulatory iPSC-derived non-lymphoid progeny in autoimmunity and GVHD alloimmunity

Jordan N. Fink, Yao Ke, Cameron McDonald-Hyman, Phillip M. Dougherty et autres

Non-lymphoid immunoregulatory cells, including mesenchymal stem cells (MSCs), myeloid-derived suppressor cells (MDSCs), regulatory macrophages (Mregs), and tolerogenic dendritic cells (Tol-DCs), play critical roles in maintaining immune homeostasis. However, their therapeutic application in autoimmune diseases and graft-versus-host disease (GVHD) has received comparatively less …

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Targeting cell-surface VISTA expression on allospecific naïve T cells promotes tolerance

Brent H. Koehn, Elizabeth C. Nowak, Sladjana Skopalja-Gardner, Asim Saha et autres

ABSTRACT: The success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be limited by graft-versus-host disease (GVHD). T-cell activation is a key factor in GVHD progression. Costimulatory signals can be counterbalanced by coinhibitory signals such as the checkpoint molecule VISTA (V-domain immunoglobulin-containing …

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Deficiency of T follicular helper cell Tet3 DNA demethylation inhibits pathogenic IgG2c class switching and chronic GVHD

Michael Zaiken, Sujeong Jin, Cameron McDonald-Hyman, Christina R. Hartigan et autres

ABSTRACT: Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse-associated mortality after allogeneic hematopoietic cell transplantation. Treating steroid resistant/refractory cGVHD remains challenging. Epigenetic regulators can have global transcriptional effects that control donor T-cell responses. We previously showed that inhibiting …

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The role of VISTA engagement in limiting neutrophil-mediated inflammation

Elizabeth C. Nowak, Jiannan Li, Mohamed ElTanbouly, Wilson L. Davis et autres

Abstract A growing body of evidence suggests that VISTA, an immune checkpoint inhibitory receptor, plays a central role in the regulation of innate immunity in the settings of inflammatory diseases and cancer. Neutrophils are among the cells that have the highest membrane …

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Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severity

Jemma H. Larson, Sujeong Jin, Michaël Loschi, Sara Bolivar-Wagers et autres

Damage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor to the severity and perpetuation of graft-versus-host disease. In preclinical models and clinical trials, we showed that infusing high numbers of regulatory T cells reduces graft-versus-host disease …

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Insights and strategies to promote immune tolerance in allogeneic hematopoietic stem cell transplantation recipients

Govindarajan Thangavelu, Sara Bolivar-Wagers, Ethan G. Aguilar, Stephanie Y. Rhee et autres

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Contributors

Ethan G. Aguilar, Farah Asa’ad, Kiandokht Bashiri, Rasheedunnisa Begum et autres

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Prevention of acute GVHD using an orthogonal IL-2/IL-2Rβ system to selectively expand regulatory T cells in vivo

Teresa Lopes Ramos, Sara Bolivar-Wagers, Sujeong Jin, Govindarajan Thangavelu et autres

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but …

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Murine CAR19 Tregs suppress acute graft-versus-host disease and maintain graft-versus-tumor responses

Sara Bolivar-Wagers, Michaël Loschi, Sujeong Jin, Govindarajan Thangavelu et autres

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) efficacy is complicated by graft-versus-host disease (GVHD), a leading cause of morbidity and mortality. Regulatory T cells (Tregs) have shown efficacy in preventing GVHD. However, high Treg doses are often required, necessitating substantial ex vivo or …

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Dual JAK2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair

Kelly Walton, Kirsti L. Walker, Megan Riddle, Brent H. Koehn et autres

Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and …

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