Single cell profiling of hematopoietic stem cell transplant recipients reveals TGF-β1 and IL-2 confer immunoregulatory functions to NK cells

Autor: Jessica A. Mathews, Dorota T. Borovsky, Kyle T. Reid, Julia M. Murphy, Sarah J. Colpitts, Abel Santos Carreira, Tommy Alfaro Moya, Douglas C. Chung, Igor Novitzky-Basso, Jonas Mattsson, Pamela S. Ohashi, Sarah Q. Crome
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 12, Pp 111416- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.111416
Popis: Summary: Natural killer (NK) cell activity is influenced by cytokines and microenvironment factors, resulting in remarkably diverse functions, by contributing to inflammatory responses or serving as rheostats of adaptive immunity. Using single cell RNA sequencing (scRNA-seq), we identified a TGFβ1highCD56brightNK cell population associated with hematopoietic stem cell transplant recipients protected from acute graft-versus-host disease (GVHD). We further define a role for the combination of interleukin-2 (IL-2) and transforming growth factor β1 (TGF-β1) in promoting a regulatory phenotype in NK cells. “Induced” regulatory NK cells produce high amounts of TGF-β1, inhibited T cells, could promote naive T cells differentiation into regulatory T cells, and exhibited a unique transcriptional program that includes expression of IKZF2 (HELIOS) and ZNF683 (HOBIT). This phenotype was not stable, and “induced” regulatory NK cells lost the ability to secrete TGF-β1 upon exposure to different cytokines. These findings define protective CD56brightNK cells post-hematopoietic stem cell transplantation, and demonstrate the combination of IL-2 and TGF-β1 promotes regulatory activity in NK cells.
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