The role of IL-9-mediated T-cell senescence in ILC-driven prevention of GVHD
Tufa DM, Hoffmeyer E, Schaller KL, et al. Innate Lymphoid Cells Prevent Graft-Versus-Host Disease Via IL-9-Driven T-Cell Senescence. Blood. 2025; (doi: 10.1182/blood.2025028504).
Innate lymphoid cells (ILCs) derived from hematopoietic stem cells mitigate graft-versus-host disease (GVHD) in human and mice models but, until now, how they do so has not been fully understood. In their exploration of this dynamic, researchers observed that ILCs — lymphocytes that regulate tissue homeostasis and immune responses — produce the cytokine IL-9 and curb T cell proliferation. Importantly, ILCs also promote T-cell senescence by upregulating related surface receptors and by increasing expression of senescence-related proteins when interacting with T cells. Introducing exogenous IL-9 to T cells results in similar outcomes; however, cytokine inhibition effectively blocks T-cell senescence.