Mathews Jessica A, Borovsky Dorota T, Reid Kyle T, Murphy Julia M, Colpitts Sarah J, Carreira Abel Santos, Moya Tommy Alfaro, Chung Douglas C, Novitzky-Basso Igor, Mattsson Jonas, Ohashi Pamela S, Crome Sarah Q
Toronto General Hospital Research Institute, Ajmera Transplant Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
iScience. 2024 Nov 18;27(12):111416. doi: 10.1016/j.isci.2024.111416. eCollection 2024 Dec 20.
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 CD56NK 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 (HELIOS) and (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 CD56NK cells post-hematopoietic stem cell transplantation, and demonstrate the combination of IL-2 and TGF-β1 promotes regulatory activity in NK cells.
自然杀伤（NK）细胞的活性受细胞因子和微环境因素的影响，通过参与炎症反应或作为适应性免疫的调节器，其功能表现出显著的多样性。利用单细胞RNA测序（scRNA-seq），我们鉴定出了一群与免受急性移植物抗宿主病（GVHD）的造血干细胞移植受者相关的CD56⁺NK细胞群体。我们进一步确定了白细胞介素-2（IL-2）和转化生长因子β1（TGF-β1）的组合在促进NK细胞调节表型中的作用。“诱导性”调节性NK细胞产生大量TGF-β1，抑制T细胞，可促进初始T细胞分化为调节性T细胞，并表现出独特的转录程序，包括（HELIOS）和（HOBIT）的表达。这种表型不稳定，“诱导性”调节性NK细胞在暴露于不同细胞因子后会失去分泌TGF-β1的能力。这些发现明确了造血干细胞移植后具有保护作用的CD56⁺NK细胞，并证明IL-2和TGF-β1的组合可促进NK细胞的调节活性。
