Caractérisation phénotypique et fonctionnelle des cellules NK en contexte physiologique et néoplasique
NK cells are part of the innate immune system and participate in anti-tumor immunosurveillance. Understanding the factors affecting their biology, such as genetics, is therefore crucial. First, we evaluated the role of the integrin subunit CD11d on the phenotype and expression of other subunits (CD11a, CD11b, CD11c, CD18) of various immune cells between a CD11d-KO mouse model and a C57BL/6 (B6) mouse. We noted that the effect of CD11d deletion on the expression of other integrin subunits is specific to each immune cell type. The most notable difference in CD11b and CD11c expression was observed in NK cells. Loss of CD11d in NK cells resulted in decreased CD107a expression after their activation, suggesting impaired NK cell degranulation. Second, despite similar melanoma growth, a greater proportion of CD11d-KO-derived NK cells accumulated in tumor beds compared to their B6 counterpart. We then exploited the NOD mouse model, known to have significant immune defects. The acquisition of cytotoxic functions of NK cells occurs through a process called functional maturation where an NK cell is first CD27-CD11b-, followed by the CD27+CD11b- stage, then CD27+CD11b+ and finally CD27-CD11b+, the most mature and cytotoxic stage. We demonstrated that NK cells from NOD mice produce significantly less IFN-γ, TNFα, and Granzyme B and fail to regulate the expression of the activation receptor NKG2D for each stage of functional maturation. Finally, we treated immunodeficient tumor-bearing mice with NOD and B6 NK cells. We demonstrated that, as with B6 NK cells, NOD CD27+ NK cells predominantly accumulated in tumors. However, mice injected with NOD NK cells showed significantly greater tumor growth.  Overall, these studies are the first to elucidate the impact of the absence of CD11d on the phenotype and function of NK cells as well as their functional defects in NOD mice during their functional maturation.
cellule Natural Killer NK CD11d souris Non-Obese Diabetic Natural Killer cell integrin CD11d Non-Obese Diabetic mouse functional maturation