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NK Cell Subsets in Health and Disease: New Developments

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453504 Year: Pages: 243 DOI: 10.3389/978-2-88945-350-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-02-27 16:16:45
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Natural Killer (NK) cells were discovered ca 1975, as the first group of lymphoid cells that were neither T cells nor B cells. Since then, the dissection of the biology of NK cells has been growing exponentially with many seminal discoveries from the identification of MHC class I-specific inhibitory receptors to the discovery of receptor-ligand pairs involved in NK cell activation and to the manipulation of NK cells in cancer. In this research topic, we asked a group of thought leaders in NK cell biology to review recent advances in their origins and biology, and their roles in cancer, infection and inflammation. Together, these 25 articles provide a timely survey of NK cells as critical immunologic components of health and disease. They will hopefully prompt further dialogue and developments in basic and translational immunology.

Evolution of NK-mediated target recognition under the pressure of physiologic or pathologic stimuli

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194520 Year: Pages: 190 DOI: 10.3389/978-2-88919-452-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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Since their discovery NK cells have come out as potential tools to fight cancer and viruses. This finding early urged different groups to study the mechanisms governing NK cell function. The identification of the MHC-I-specific inhibitory receptors (i.e. KIRs, NKG2A and certain Ly49 molecules) allowed defining rather rapidly how NK cells could avoid self-aggression and how they could be directed towards targets that were forced, by viral infection or tumor transformation, to down-regulate MHC-I expression. In a second time, also the repertoire of surface activating receptors addressing NK cytotoxicity towards tumors and pathogens was mostly defined. In spite of the first findings, however, most recent studies may suggest that NK cells and their receptors might not have been evolved to kill tumor targets and, perhaps, they might have been only partially influenced, in their evolution, by the need of recognizing viruses. Indeed certain NK receptors known to activate NK cell cytotoxicity (NKp30, DNAM-1, NKp80) can also participate at regulatory interactions occurring between NK and myeloid cells. In addition, a peculiar NK cell subset which intensively populate decidua during the first trimester of pregnancy, through the engagement of specific receptors and the interaction with decidual DC, produce chemokines and pro-angiogenic cytokines, and induce Tregs. Thus, in this context, NK cells favor decidua vascularization and development of the (semiallogeneic) foetus in a tolerant environment. Viruses have nevertheless played an important role in shaping the NK cell receptor repertoire. Several studies have unveiled clues of the evolutionary struggle between these pathogens and NK cells. Different NK receptors, including NKp46, NKp30, NKp44, NKG2D, NKG2C, Ly49, and certain KIRs have been demonstrated to recognize virus-encoded or virus-induced ligands. The expression of TLR specifically recognizing microbial products, together with the unexpected role of KIR3DL2 in shuttling these products to TLR-containing endosomes have also been documented in NK cells. On the other side, different viral immune evasion molecules have been shown to interfere with the expression of ligands for T or NK cell activating receptors. In addition, viral infections can occur in the reproductive stage of life cycle, and may represent a serious threat for the species propagation. Thus the control of viruses, together with the maintenance of foetus during pregnancy, should represent major evolutionary forces in shaping NK-receptors. Along this line, the NK-mediated control of tumors should not be under the same evolutionary pressure, as tumors mostly appear later in the life cycle, and the recognition of tumor-encoded ligands may be less efficient (as the NK cell receptors might have not been selected for such aim). This may be the reason why, although displaying strong antitumor activity in vitro, NK cells could hardly contain tumor burden in vivo. In addition the pathogen-driven evolution of NK cell function may also favor the role of NK cells in the insurgence of immune-mediated diseases. This research topic will collect contributions that may clarify the relationships between the evolution of the NK receptors and their role in an efficient recognition of viruses and tumor cells or in immune-mediated diseases.

Lymphocytes in MS and EAE: More than just a CD4+ World

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453023 Year: Pages: 160 DOI: 10.3389/978-2-88945-302-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-02-27 16:16:45
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Multiple sclerosis is degenerative disease of the central nervous system (CNS) in which myelin destruction and axon loss leads to the accumulation of physical, cognitive, and mental deficits. MS affects more than a million people worldwide and managing this chronic disease presents a significant health challenge. Multiple lines of evidence indicate that MS is an autoimmune disorder in which immune cells launch an inflammatory attack targeting myelin antigens. Indeed, myelin-reactive T cells and antibodies have been identified in MS patients and in animal models (namely experimental autoimmune encephalomyelitis, or EAE) that recapitulate many features of human disease. Animal model studies have demonstrated that T cells are both necessary and sufficient to initiate and sustain CNS autoimmunity. However, most MS animal models rely on the role played by CD4+ T cells and partially replicate the multiple aspects of MS pathogenesis. Thus, research in the past has focused heavily on the contribution of CD4+ T cells to the disease process; searching PubMed for “MS AND CD4” yields twice the results as corresponding searches for “CD8” or “B cell” and four times that for “NK cells”. While CD4+ T cells may represent the minimum requirement to mediate CNS autoimmunity, it is clear that the immune response underlying human MS is far more complex and involves numerous other immune cells and subsets. This is well illustrated by the observation that MS patients treated with an anti-CD4 depleting antibody did not gain any clinical benefits whereas removal of several lymphocyte subsets using an anti-CD52 depleting antibody has been shown to impede disease progression. In particular, the pathogenic role(s) of non-CD4+ T cell lymphocytes is relatively poorly understood and under-researched, despite evidence that these subsets contribute to disease pathology or regulation. For example, the observed oligoclonal expansion of CD8+ T cells within the CNS compartment supports a local activation. CD8+ T cells with polarized cytolytic granules are seen in close proximity to oligodendrocytes and demyelinated axons in MS tissues. The presence of B cells in inflammatory lesions and antibodies in the CSF have long been recognized as features of MS and Rituximab, a B cell depleting therapy, has been shown to be highly effective to treat MS. Intriguingly, the putative MS therapeutic reagent Daclizumab may function in part through the expansion of a subset of immunoregulatory NK cells. NKT and ?d T cells may also play a role in CNS autoimmunity, given that they respond to lipid antigens and that myelin is lipid-rich. While different animal models recapitulate some of these aspects of human disease, identifying appropriate models and measures to investigate the role of these less well-understood lymphocytes in MS remains a challenge for the field. This Frontiers research topic aims to create a platform for both animal- and human-focused researchers to share their original data, hypotheses, future perspectives and commentaries regarding the role of these less-well understood lymphocyte subsets (CD8+ T cells, B cells, NK cells, NK T cells, ?d T cells) in the pathogenesis of CNS autoimmunity.

The Second Life of Natural Killer (NK) Cells

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455461 Year: Pages: 118 DOI: 10.3389/978-2-88945-546-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:42
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Natural Killer (NK) cells are innate lymphocytes, now recognized as members of a larger family of “Innate lymphoid cells” (ILCs). Both murine and human NK cells are well characterized effector cells with cytotoxic as well as cytokine production ability which mainly react in response to microbial and cell stress stimuli, thus playing a central role in the defense against pathogen infection, in tumor surveillance and in regulating immune homeostasis. Despite these established concepts, our understanding of the complexity of NK cells, also in view of their developmental and functional relationship with other ILC subsets, is only recently emerging. This Research Topic highlights the recent advances in NK cell (and ILC) research in human and mouse from basic research to clinical applications.

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