التفاصيل البيبلوغرافية
العنوان: |
Analysis of the mechanisms regulating soluble PD-1 production and function in human NK cells |
المؤلفون: |
Mariotti, Francesca Romana, Ingegnere, Tiziano, Landolina, Nadine, Vacca, Paola, Munari, Enrico, Moretta, Lorenzo |
المساهمون: |
Fondazione AIRC per la ricerca sul cancro ETS, Ministry of Health, HORIZON EUROPE Marie Sklodowska-Curie Actions |
المصدر: |
Frontiers in Immunology ; volume 14 ; ISSN 1664-3224 |
بيانات النشر: |
Frontiers Media SA |
سنة النشر: |
2023 |
المجموعة: |
Frontiers (Publisher - via CrossRef) |
مصطلحات موضوعية: |
Immunology, Immunology and Allergy |
الوصف: |
NK cells represent important effectors that play a major role in innate defences against pathogens and display potent cytolytic activity against tumor cells. An array of surface receptors finely regulate their function and inhibitory checkpoints, such as PD-1, can dampen the immune response inducing an immunosuppressive state. Indeed, PD-1 expression in human NK cells correlated with impaired effector function and tumor immune evasion. Importantly, blockade of the PD-1/PD-L1 axis has been shown to reverse NK cell exhaustion and increase their cytotoxicity. Recently, soluble counterparts of checkpoint receptors, such as soluble PD-1 (sPD-1), are rising high interest due to their biological activity and ability to modulate immune responses. It has been widely demonstrated that sPD-1 can modulate T cell effector functions and tumor growth. Tumor-infiltrating T cells are considered the main source of circulating sPD-1. In addition, recently, also stimulated macrophages have been demonstrated to release sPD-1. However, no data are present on the role of sPD-1 in the context of other innate immune cell subsets and therefore this study is aimed to unveil the effect of sPD-1 on human NK cell function. We produced the recombinant sPD-1 protein and demonstrated that it binds PD-L1 and that its presence results in increased NK cell cytotoxicity. Notably, we also identified a pathway regulating endogenous sPD-1 synthesis and release in human NK cells. Secreted endogenous sPD-1, retained its biological function and could modulate NK cell effector function. Overall, these data reveal a pivotal role of sPD-1 in regulating NK-mediated innate immune responses. |
نوع الوثيقة: |
article in journal/newspaper |
اللغة: |
unknown |
DOI: |
10.3389/fimmu.2023.1229341 |
DOI: |
10.3389/fimmu.2023.1229341/full |
الإتاحة: |
https://doi.org/10.3389/fimmu.2023.1229341Test |
حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
رقم الانضمام: |
edsbas.68B23FAE |
قاعدة البيانات: |
BASE |