Interleukin 15 Primes Natural Killer Cells to Kill via NKG2D and cPLA2 and This Pathway Is Active in Psoriatic Arthritis

NK cells are large granular lymphocytes that form a critical component of the innate immune system, whose functions include the killing of cells expressing stress-induced molecules. It is increasingly accepted that despite being considered prototypical effector cells, NK cells require signals to reach their full cytotoxic potential. We previously showed that IL-15 is capable of arming CD8 effector T cells to kill independently of their TCR via NKG2D in a cPLA2-dependent process. As NK cells also express NKG2D, we wanted to investigate whether this pathway functioned in an analogous manner and if resting NK cells could be primed to the effector phase by IL-15. Furthermore, to establish relevance to human disease we studied a possible role for this pathway in the pathogenesis of psoriatic arthritis, since there are aspects of this disease that suggest a potential effector role for the innate immune system. We found that PsA patients had upregulated IL-15 and MIC in their affected synovial tissues, and that this unique inflammatory environment enabled NK cell activation and killing via NKG2D and cPLA2. Moreover, we were able to reproduce the phenotype of joint NK cells from blood NK cells by incubating them with IL-15. Altogether, these findings suggest a destructive role for NK cells when activated by environmental stress signals during the pathogenesis of PsA and demonstrate that IL-15 is capable of priming resting NK cells in tissues to the effector phase.</p

Interleukin 15 Primes Natural Killer Cells to Kill via NKG2D and cPLA2 and This Pathway Is Active in Psoriatic Arthritis

NK cells are large granular lymphocytes that form a critical component of the innate immune system, whose functions include the killing of cells expressing stress-induced molecules. It is increasingly accepted that despite being considered prototypical effector cells, NK cells require signals to reach their full cytotoxic potential. We previously showed that IL-15 is capable of arming CD8 effector T cells to kill independently of their TCR via NKG2D in a cPLA2-dependent process. As NK cells also express NKG2D, we wanted to investigate whether this pathway functioned in an analogous manner and if resting NK cells could be primed to the effector phase by IL-15. Furthermore, to establish relevance to human disease we studied a possible role for this pathway in the pathogenesis of psoriatic arthritis, since there are aspects of this disease that suggest a potential effector role for the innate immune system. We found that PsA patients had upregulated IL-15 and MIC in their affected synovial tissues, and that this unique inflammatory environment enabled NK cell activation and killing via NKG2D and cPLA2. Moreover, we were able to reproduce the phenotype of joint NK cells from blood NK cells by incubating them with IL-15. Altogether, these findings suggest a destructive role for NK cells when activated by environmental stress signals during the pathogenesis of PsA and demonstrate that IL-15 is capable of priming resting NK cells in tissues to the effector phase

Epidermal Langerhans Cells-A Target for HTLV-III/LAV Infection

Langerhans cells (LC) are bone marrow-derived, la+, CD1+, CD4+, ATPase+ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV-seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17+ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as well as cytopathic changes in approximately one-third of the LC population were demonstrated by electron microscopy. These results strongly suggest that LC may harbor HTLV-III/LAV. The infection of LC with this retrovirus may have deleterious consequences for the immunologic functions of this cell system and may thus contribute to both the acquisition of immunodeficiency and the infectious and neoplastic complications of AIDS

Normally occurring NKG2D+CD4+ T cells are immunosuppressive and inversely correlated with disease activity in juvenile-onset lupus

The NKG2D receptor stimulates natural killer cell and T cell responses upon engagement of ligands associated with malignancies and certain autoimmune diseases. However, conditions of persistent NKG2D ligand expression can lead to immunosuppression. In cancer patients, tumor expression and shedding of the MHC class I–related chain A (MICA) ligand of NKG2D drives proliferative expansions of NKG2D+CD4+ T cells that produce interleukin-10 (IL-10) and transforming growth factor-β, as well as Fas ligand, which inhibits bystander T cell proliferation in vitro. Here, we show that increased frequencies of functionally equivalent NKG2D+CD4+ T cells are inversely correlated with disease activity in juvenile-onset systemic lupus erythematosus (SLE), suggesting that these T cells may have regulatory effects. The NKG2D+CD4+ T cells correspond to a normally occurring small CD4 T cell subset that is autoreactive, primed to produce IL-10, and clearly distinct from proinflammatory and cytolytic CD4 T cells with cytokine-induced NKG2D expression that occur in rheumatoid arthritis and Crohn's disease. As classical regulatory T cell functions are typically impaired in SLE, it may be clinically significant that the immunosuppressive NKG2D+CD4+ T cells appear functionally uncompromised in this disease

Adenovirus vector delivery stimulates natural killer cell recognition

We report that delivery of first-generation replication-deficient adenovirus (RDAd) vectors into primary human fibroblasts is associated with the induction of natural killer (NK) cell-mediated cytolysis in vitro. RDAd vector delivery induced cytolysis by a range of NK cell populations including the NK cell clone NKL, primary polyclonal NK lines and a proportion of NK clones (36 %) in autologous HLA-matched assays. Adenovirus-induced cytolysis was inhibited by antibody blocking of the NK-activating receptor NKG2D, implicating this receptor in this function. NKG2D is ubiquitously expressed on NK cells and CD8+ T cells. Significantly, γ-irradiation of the vector eliminated the effect, suggesting that breakthrough expression from the vector induces at least some of the pro-inflammatory responses of unknown aetiology following the application of RDAd vectors during in vivo gene delivery

Soil moisture observation in a forested headwater catchment: combining a dense cosmic-ray neutron sensor network with roving and hydrogravimetry at the TERENO site Wüstebach

Cosmic-ray neutron sensing (CRNS) has become an effective method to measure soil moisture at a horizontal scale of hundreds of metres and a depth of decimetres. Recent studies proposed operating CRNS in a network with overlapping footprints in order to cover root-zone water dynamics at the small catchment scale and, at the same time, to represent spatial heterogeneity. In a joint field campaign from September to November 2020 (JFC-2020), five German research institutions deployed 15 CRNS sensors in the 0.4 km2 Wüstebach catchment (Eifel mountains, Germany). The catchment is dominantly forested (but includes a substantial fraction of open vegetation) and features a topographically distinct catchment boundary. In addition to the dense CRNS coverage, the campaign featured a unique combination of additional instruments and techniques: hydro-gravimetry (to detect water storage dynamics also below the root zone); ground-based and, for the first time, airborne CRNS roving; an extensive wireless soil sensor network, supplemented by manual measurements; and six weighable lysimeters. Together with comprehensive data from the long-term local research infrastructure, the published data set (available at https://doi.org/10.23728/b2share.756ca0485800474e9dc7f5949c63b872; Heistermann et al., 2022) will be a valuable asset in various research contexts: to advance the retrieval of landscape water storage from CRNS, wireless soil sensor networks, or hydrogravimetry; to identify scale-specific combinations of sensors and methods to represent soil moisture variability; to improve the understanding and simulation of land–atmosphere exchange as well as hydrological and hydrogeological processes at the hillslope and the catchment scale; and to support the retrieval of soil water content from airborne and spaceborne remote sensing platforms

Soil moisture observation in a forested headwater catchment: combining a dense cosmic-ray neutron sensor network with roving and hydrogravimetry at the TERENO site Wüstebach

Cosmic-ray neutron sensing (CRNS) has become an effective method to measure soil moisture at a horizontal scale of hundreds of metres and a depth of decimetres. Recent studies proposed operating CRNS in a network with overlapping footprints in order to cover root-zone water dynamics at the small catchment scale and, at the same time, to represent spatial heterogeneity. In a joint field campaign from September to November 2020 (JFC-2020), five German research institutions deployed 15 CRNS sensors in the 0.4 km2 Wüstebach catchment (Eifel mountains, Germany). The catchment is dominantly forested (but includes a substantial fraction of open vegetation) and features a topographically distinct catchment boundary. In addition to the dense CRNS coverage, the campaign featured a unique combination of additional instruments and techniques: hydro-gravimetry (to detect water storage dynamics also below the root zone); ground-based and, for the first time, airborne CRNS roving; an extensive wireless soil sensor network, supplemented by manual measurements; and six weighable lysimeters. Together with comprehensive data from the long-term local research infrastructure, the published data set (available at https://doi.org/10.23728/b2share.756ca0485800474e9dc7f5949c63b872; Heistermann et al., 2022) will be a valuable asset in various research contexts: to advance the retrieval of landscape water storage from CRNS, wireless soil sensor networks, or hydrogravimetry; to identify scale-specific combinations of sensors and methods to represent soil moisture variability; to improve the understanding and simulation of land–atmosphere exchange as well as hydrological and hydrogeological processes at the hillslope and the catchment scale; and to support the retrieval of soil water content from airborne and spaceborne remote sensing platforms

Soil moisture observation in a forested headwater catchment: combining a dense cosmic-ray neutron sensor network with roving and hydrogravimetry at the TERENO site Wüstebach

Cosmic-ray neutron sensing (CRNS) has become an effective method to measure soil moisture at a horizontal scale of hundreds of metres and a depth of decimetres. Recent studies proposed operating CRNS in a network with overlapping footprints in order to cover root-zone water dynamics at the small catchment scale and, at the same time, to represent spatial heterogeneity. In a joint field campaign from September to November 2020 (JFC-2020), five German research institutions deployed 15 CRNS sensors in the 0.4 km2 Wüstebach catchment (Eifel mountains, Germany). The catchment is dominantly forested (but includes a substantial fraction of open vegetation) and features a topographically distinct catchment boundary. In addition to the dense CRNS coverage, the campaign featured a unique combination of additional instruments and techniques: hydro-gravimetry (to detect water storage dynamics also below the root zone); ground-based and, for the first time, airborne CRNS roving; an extensive wireless soil sensor network, supplemented by manual measurements; and six weighable lysimeters. Together with comprehensive data from the long-term local research infrastructure, the published data set (available at https://doi.org/10.23728/b2share.756ca0485800474e9dc7f5949c63b872; Heistermann et al., 2022) will be a valuable asset in various research contexts: to advance the retrieval of landscape water storage from CRNS, wireless soil sensor networks, or hydrogravimetry; to identify scale-specific combinations of sensors and methods to represent soil moisture variability; to improve the understanding and simulation of land–atmosphere exchange as well as hydrological and hydrogeological processes at the hillslope and the catchment scale; and to support the retrieval of soil water content from airborne and spaceborne remote sensing platforms

Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15

IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A2 (cPLA2) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC+ target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA2 activation and AA release. Finally, cPLA2 activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA2 activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets