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n the last years, our knowledge of human NK cell biology has increased significantly. Several stimulating studies have provided the basis for understanding how NK cells can be “educated” to acquire immunological competence following maturation, or to adapt their function to the environmental changes of “self”. New information has been acquired on their lifespan and on the persistence of memory-like NK cell subsets in response to certain viral infections. In addition, the identification and characterization of new markers and the development of more effective analytic approaches have led to the definition of various phenotypically and/or functionally-defined cell subsets. These advances have, in turn, enabled us to study NK cells beyond the peripheral blood, in different tissue compartments including the bone marrow, liver, lungs, skin, intestine and uterus. Recent data indicates that at least part of the tissue NK cell compartment consists of resident cells (which rarely recirculate) characterized by tissue-specific phenotypes and, in some cases, endowed with specialized functions related to the distinct organs in which they reside. These findings stimulate further questions (i) on the origins of these putative tissue-specific NK cell subsets; (ii) on their functional interplay with the local microenvironment; (iii) on their immunological competence and memory capacity and (iv) on their possible specific functional role in healthy and diseased tissues. In this context, the assessment of phenotype, function, maturation, education, differentiation and reprogramming of effector functions in tissue NK cells represents a new stimulating field of investigation that would help to get a more comprehensive picture of NK cell biology. In this Research Topic, we collect articles that highlight the recent advances in our understanding of tissue NK cells and that provide insight into opening new viewpoints on the role of NK cells in both health and disease.

Medicine --- Immunology --- conventional NK cells --- tissue resident NK cells --- innate lymphoid cells --- tissue microenvironment --- NK receptors

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n the last years, our knowledge of human NK cell biology has increased significantly. Several stimulating studies have provided the basis for understanding how NK cells can be “educated” to acquire immunological competence following maturation, or to adapt their function to the environmental changes of “self”. New information has been acquired on their lifespan and on the persistence of memory-like NK cell subsets in response to certain viral infections. In addition, the identification and characterization of new markers and the development of more effective analytic approaches have led to the definition of various phenotypically and/or functionally-defined cell subsets. These advances have, in turn, enabled us to study NK cells beyond the peripheral blood, in different tissue compartments including the bone marrow, liver, lungs, skin, intestine and uterus. Recent data indicates that at least part of the tissue NK cell compartment consists of resident cells (which rarely recirculate) characterized by tissue-specific phenotypes and, in some cases, endowed with specialized functions related to the distinct organs in which they reside. These findings stimulate further questions (i) on the origins of these putative tissue-specific NK cell subsets; (ii) on their functional interplay with the local microenvironment; (iii) on their immunological competence and memory capacity and (iv) on their possible specific functional role in healthy and diseased tissues. In this context, the assessment of phenotype, function, maturation, education, differentiation and reprogramming of effector functions in tissue NK cells represents a new stimulating field of investigation that would help to get a more comprehensive picture of NK cell biology. In this Research Topic, we collect articles that highlight the recent advances in our understanding of tissue NK cells and that provide insight into opening new viewpoints on the role of NK cells in both health and disease.

Medicine --- Immunology --- conventional NK cells --- tissue resident NK cells --- innate lymphoid cells --- tissue microenvironment --- NK receptors --- conventional NK cells --- tissue resident NK cells --- innate lymphoid cells --- tissue microenvironment --- NK receptors

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Medicine --- Immunology --- NK cells --- NK cell-based immunotherapy --- cancer immunotherapy --- immune checkpoint inhibitors --- adoptive transfer of NK and CAR-NK cells --- ligands for NK cell-activating receptors

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More than 90% of diseases possess immunological abnormalities. Disorders such as inflammation, hypersensitivity, autoimmunity and immunodeficiency are simple examples of how the immune system misinterprets its surroundings and goes awry. Multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, among many others are manifestations of immune cells attacking normal tissues. On the other hand, damping the immune system leads to diseases such as cancer, AIDS, and severe combined immunodeficiency. The last ten years witnessed an explosion in developing drugs that target the immune system. Several novel monoclonal antibodies have been approved for treatment of various diseases confirming that personalized medicine approach is robust in combating diseases. Hence, the future holds great promise for using personalized and targeted medicine rather than generalized medications that, in most circumstances, proven to be ineffective and characteristically exert side effects. Approaches such as generating novel adjuvants that can stimulate the immune system without harmful side effects, targeting inflammatory cytokines and chemokines, harnessing and activating innate immune cells such as natural killer cells or dendritic cells, are examples of future approaches to treat autoimmune diseases, AIDS, and various forms of cancer resulting from chronic inflammation. More recently, targeting immune checkpoint molecules have shown therapeutic response against lung cancer and melanoma. Identifying molecules involved in autophagy is another example of how personalized medicine might help treat patients with refractory asthma and autoimmune diseases. This topic introduces the reader to these novel approaches of manipulating the immune system and developing targeted therapeutic strategies for treatment of various diseases.

Drugs --- Multiple sclerosis --- NK cells --- Leukemia --- AIDS --- Adjuvants --- Lymphoma --- Autophagy --- Chemokines --- Cancer --- Drugs --- Multiple sclerosis --- NK cells --- Leukemia --- AIDS --- Adjuvants --- Lymphoma --- Autophagy --- Chemokines --- Cancer

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Medicine --- Immunology --- immune crosstalk --- lymphocytes --- T-cells --- NK cells --- dendritic cells --- immunotherapy --- cancer --- infections --- immune crosstalk --- lymphocytes --- T-cells --- NK cells --- dendritic cells --- immunotherapy --- cancer --- infections