title: Dysregulation of Chemokine/Chemokine Receptor Axes and NK Cell Tissue Localization during Diseases.
abstract: Chemokines are small chemotactic molecules that play key roles in physiological and pathological conditions. Upon signalingviatheir specific receptors, chemokines regulate tissue mobilization and trafficking of a wide array of immune cells, including natural killer (NK) cells. Current research is focused on analyzing changes in chemokine/chemokine receptor expression during various diseases to interfere with pathological trafficking of cells or to recruit selected cell types to specific tissues. NK cells are a heterogeneous lymphocyte population comprising several subsets endowed with distinct functional properties and mainly representing distinct stages of a linear development process. Because of their different functional potential, the type of subset that accumulates in a tissue drives the final outcome of NK cell-regulated immune response, leading to either protection or pathology. Correspondingly, chemokine receptors, including CXCR4, CXCR3, and CX3CR1, are differentially expressed by NK cell subsets, and their expression levels can be modulated during NK cell activation. At first, this review will summarize the current knowledge on the contribution of chemokines to the localization and generation of NK cell subsets in homeostasis. How an inappropriate chemotactic response can lead to pathology and how chemokine targeting can therapeutically affect tissue recruitment/localization of distinct NK cell subsets will also be discussed.
authors.affiliation: Department of Molecular Medicine, Sapienza University, Rome, Italy; IRCCS NEUROMED - Mediterranean Neurological Institute, Isernia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bernardini
authors.affiliation: Department of Molecular Medicine, Sapienza University , Rome , Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Antonangeli
authors.affiliation: Department of Molecular Medicine, Sapienza University , Rome , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bonanni
authors.affiliation: IRCCS NEUROMED - Mediterranean Neurological Institute, Isernia, Italy; Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
keywords: CXCR3; CXCR4; NK cell subsets; chemokine receptors; cross-inhibition; migration; multiple myeloma; multiple sclerosis