Characterization of the perturbed memory NK cell pool in autoantibody-driven autoimmune disease
|Davide De Federicis||Dottorando/Assegnista/Specializzando componente il gruppo di ricerca|
|Ricciarda Galandrini||Aggiungi Tutor di riferimento (Professore o Ricercatore afferente allo stesso Dipartimento del Proponente)|
Natural Killer (NK) cells represent a pivotal player of innate immune responses, and may also positively or negatively affect the development, breadth and persistence of adaptive responses. NK cells may contribute to immune homeostasis and to the pathogenesis of autoimmune diseases by producing cytokines and chemokines, and through direct cell-cell interactions with dendritic cells (DC) and T cells. The impact of environmental factors on NK cell compartment is increasingly appreciated. Human Cytomegalovirus (HCMV) infection induces the expansion of a long-lived, phenotypically heterogeneous, "memory" NK cell population, characterized by enhanced CD16 (low affinity receptor for IgG)-dependent functional capabilities, in a fraction of seropositive subjects. The mechanisms that regulate memory NK cell pool size, long-term persistence, and activation have not been fully characterized yet. Chronic interaction with IgG-opsonized cells may represent an efficient stimulus for memory NK cell expansion and/or maintenance in vivo. We have recently described the perturbation of the equilibrium of the memory NK cell subsets in a cohort of HCMV+ patients affected by immune thrombocytopenia (ITP), an autoimmune disease where anti-platelet autoantibodies play a major role. We have also found that ITP, but not control, platelets selectively promote memory NK cell in vitro expansion. Memory NK cells are placed in a privileged position for exerting a regulatory role in antibody-dependent autoimmune diseases. In the present project, we will analyze several aspects of the functional profile of memory NK cell subsets in ITP patients. We will focus on cell surface and soluble molecular signals that may dictate the crosstalk of memory NK cells with DC and T cells, such as: a) the expression of immune checkpoint repertoire, b) the molecular signature relevant for survival, self-renewal advantage, and susceptibility to apoptosis, c) CD16-dependent effector functions.