IL-33 mediated expansion of host ST2+ Treg prior to allogeneic hematopoietic cell transplantation decreases macrophage and effector T cell activation reducing acute GVHD

• DOI: 10.4049/jimmunol.196.supp.140.33
• Publication Date: 2023-01-01T10:34:01Z
• Authors: Dawn K Reichenbach; Benjamin M Matta; Xiaoli Zhang; Brent Koehn; Lisa Mathews; Michelle J Smith; Colby J Feser; Robert Zeiser; Heth Roderick Tur...; Bruce R Blazar
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Abstract Graft-versus-host disease (GVHD) is the leading complication and cause of mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Recently, we reported that IL-33 released from tissue damaged during allo-HCT conditioning mediates pro-inflammatory responses by Teffector cells resulting in greater acute GVHD lethality clinical symptoms mice. However, a pleiotropic cytokine both anti-inflammatory responses. We hypothesized beneficial effects mediated could be harnessed if was present prior to inflammatory mediators conditioning. Here, demonstrate exogenous given peri (days −10 4) recipients MHC-disparate asserts its immunoregulatory properties reduced compared non-treated controls. treatment resulted expansion recipient Treg suppressive myeloid persisted post irradiation. Host depletion C57Bl/6 FoxP3-DTR mice diphtheria toxin concurrently with accelerated alone, demonstrating host were necessary for protection. Transfer deficient ST2, receptor, afforded less protection than wild-type Treg. ST2+ controlled macrophage activation prevented accumulation target tissue. Thus, expanded activated have potential as therapeutic modality prevent treat GVHD.