Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissue-inducer (LTi)-like and NKp46(+) subsets. Both depend on RORγt and aryl hydrocarbon receptor, but NKp46(+)ILC3s ...also require Notch and T-bet for their development and are transcriptionally distinct. The extent to which these subsets have unique functions, especially in the context of T cell- and B cell-sufficient mice, remains largely unclear. To investigate the specific function of NKp46(+)ILC3s among other ILC3 subsets and T cells, we generated mice selectively lacking NKp46(+)ILC3s or all ILC3s and crossed them to T cell-deficient mice, thus maintaining B cells in all mice. In mice lacking T cells, NKp46(+)ILC3s were sufficient to promote inflammatory monocyte accumulation in the anti-CD40 innate colitis model through marked production of GM-CSF. In T cell-competent mice, lack of NKp46(+)ILCs had no impact on control of intestinal C. rodentium infection, whereas lack of all ILC3s partially impaired bacterial control. Thus, NKp46(+)ILC3s have a unique capacity to promote inflammation through GM-CSF-induced accumulation of inflammatory monocytes, but are superseded by LTi-like ILC3s and T cells in controlling intestinal bacterial infection.
•When consumers perceive a combination of Human-Robot Trust and retail assistance performance in a robot or Human-Robot Trust and social intelligence, they will always demonstrate a strong intention ...to visit a robot-operated footwear store.•When consumers do not perceive Human-Robot Trust in a robot, they will never demonstrate a strong intention to visit the robot-operated store. Thus, Human-Robot Trust is a prerequisite of store patronage.•This study serves as an example of new alternative analytical methods, such as large-N Crisp-Set Qualitative Comparative Analysis, to traditional multivariate analyses.
Based upon Computers-Are-Social-Actors and Social Exchange theories, this study investigated causal configurations of Human-Robot Trust (HRT), social intelligence, and retail assistance performance of humanoid robots that may increase consumers’ intention to visit a footwear store. A pretest and main study (n = 455) were conducted with a video-based stimulus. Using Crist-Set Qualitative Comparative Analysis (csQCA), the study took a holistic approach to the emerging topic of humanoid robots, and proposed a QCA-based conceptual framework. The results revealed that consumers will always demonstrate a strong intention to visit a robot-operated store when the configurations of HRT and retail assistance performance or HRT and social intelligence are present (sufficient conditions). Most importantly, consumers will never demonstrate a strong intention to visit the store in the absence of HRT (necessary condition). This study serves as an example of new alternative analytical methods, such as large-N csQCA applications, to traditional multivariate analyses.
While signals that activate group 3 innate lymphoid cells (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Here we found that the tumor necrosis ...factor (TNF) superfamily member receptor activator of nuclear factor κB ligand (RANKL) suppressed ILC3 activity in the intestine. Deletion of RANKL in ILC3s and T cells increased C-C motif chemokine receptor 6 (CCR6)+ ILC3 abundance and enhanced production of interleukin-17A (IL-17A) and IL-22 in response to IL-23 and during infection with the enteric murine pathogen Citrobacter rodentium. Additionally, CCR6+ ILC3s produced higher amounts of the master transcriptional regulator RORγt at steady state in the absence of RANKL. RANKL-mediated suppression was independent of T cells, and instead occurred via interactions between CCR6+ ILC3s that expressed both RANKL and its receptor, RANK. Thus, RANK-RANKL interactions between ILC3s regulate ILC3 abundance and activation, suggesting that cell clustering may control ILC3 activity.
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•CCR6+ ILC3s from RorcCreTnfsf11fl/fl mice have enhanced IL-17A and IL-22 production•Loss of Tnfsf11 in ILC3s, and not T cells, leads to hyperresponsive CCR6+ ILC3s•RANKL directly suppresses ILC3s via RANK, and RANK deficiency enhances ILC3 activity•CCR6+ ILC3s lacking RANKL have increased amounts of RORγt
Although signals that activate group 3 ILCs (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Bando et al. demonstrate that the TNF superfamily member RANKL suppresses the abundance and effector functions of intestinal CCR6+ ILC3s and that RANKL-mediated suppression occurs through ILC3-ILC3 interactions.
For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental ...cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.
Innate lymphoid cells (ILCs) are important regulators of early infection at mucosal barriers. ILCs are divided into three groups based on expression profiles, and are activated by cytokines and ...neuropeptides. Yet, it remains unknown if ILCs integrate other signals in providing protection. We show that signaling through herpes virus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor superfamily, in ILC3 is important for host defense against oral infection with the bacterial pathogen Yersinia enterocolitica. HVEM stimulates protective interferon-γ (IFN-γ) secretion from ILCs, and mice with HVEM-deficient ILC3 exhibit reduced IFN-γ production, higher bacterial burdens and increased mortality. In addition, IFN-γ production is critical as adoptive transfer of wild-type but not IFN-γ-deficient ILC3 can restore protection to mice lacking ILCs. We identify the TNF superfamily member, LIGHT, as the ligand inducing HVEM signals in ILCs. Thus HVEM signaling mediated by LIGHT plays a critical role in regulating ILC3-derived IFN-γ production for protection following infection.
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•ILC3 are required for early host defense during Y. enterocolitica infection•IFN-γ from CCR6− ILC3 is essential for protection of mice from Yersinia•HVEM expression by ILC3 is important for IFN-γ production following infection•LIGHT is the ligand for HVEM signaling in regulating ILC3-derived IFN-γ production
Seo et al. find that IFN-γ-producing ILC3 in the small intestine are required for host protection against Yersinia enterocolitica infection. HVEM signaling in ILC3, mediated by the ligand LIGHT, is critical for regulating IFN-γ production for protection following infection.
The early host response to pathogens is mediated by several distinct pattern recognition receptors. Cytoplasmic RNA helicases including RIG-I and MDA5 have been shown to respond to viral RNA by ...inducing interferon (IFN) production. Previous in vitro studies have demonstrated a direct role for MDA5 in the response to members of the Picornaviridae, Flaviviridae and Caliciviridae virus families ((+) ssRNA viruses) but not to Paramyxoviridae or Orthomyxoviridae ((-) ssRNA viruses). Contrary to these findings, we now show that MDA5 responds critically to infections caused by Paramyxoviridae in vivo. Using an established model of natural Sendai virus (SeV) infection, we demonstrate that MDA5(-/-) mice exhibit increased morbidity and mortality as well as severe histopathological changes in the lower airways in response to SeV. Moreover, analysis of viral propagation in the lungs of MDA5(-/-) mice reveals enhanced replication and a distinct distribution involving the interstitium. Though the levels of antiviral cytokines were comparable early during SeV infection, type I, II, and III IFN mRNA expression profiles were significantly decreased in MDA5(-/-) mice by day 5 post infection. Taken together, these findings indicate that MDA5 is indispensable for sustained expression of IFN in response to paramyxovirus infection and provide the first evidence of MDA5-dependent containment of in vivo infections caused by (-) sense RNA viruses.
The manifestation of "Artificial Social Intelligence (ASI)" stands as a cornerstone of a social robot system development that influences users' interactions and experiences overall in the ...ever-evolving landscape of user-centric Human-Robot Interaction (HRI). Recognizing the pivotal need to evaluate a socially interactive system accurately, this paper presents a unidimensional-scale measurement of ASI that measures a focused dimension of users' perceived social intelligence in a robot, minimizes participants' fatigue to generate higher response rates, maximizes the ability to conduct user-friendly research, and enhances the ease of interpreting the results that makes it more accessible to a diverse audience. Employing a cross-disciplinary literature review, personal interviews (n = 14), and large-scale surveys (n = 2,358) consisting of its five video-based stimuli data collection process, this study adhered meticulously to numerous scale measurement procedures to develop an "ASI Lite-Scale" and validated it with multiple tests, including Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and Exploratory Graph Analysis (EGA), assessment tests of convergent, discriminant, and nomological validity, and multi-group measurement invariance analysis to establish its robustness and ability to be generalized. This study of ASI Lite-Scale provides a structured scale development manual to help fellow researchers employ this methodology and reach a wider readership, thereby fostering the development of validated scale measurements in the field of HRI.
•Humanoid Service Robots’ networks differed in structure and the three edge-weights in adoption and rejection groups.•The adoption group revealed particularly strong positive relations among ...complexity, irritation, and mistrust.•The complexity in the adoption network and co-creation enjoyment in the rejection network were central-predictors.
Drawing upon a theoretical foundation within service-dominant logic, this study analyzed multi-group networks of humanoid service robots (HSRs) and investigated the differences in the structures and relations between groups that adopted and rejected HSRs. Moreover, it explored the most important and central predictors in each network among value co-creation and co-destruction potentials. A pretest and the main data collection (n = 474) were conducted with a video-based stimulus in an apparel store. The results revealed that the structure and the three edge-weights in the networks of the groups that adopted and rejected HSRs differed significantly. Essentially, complexity and co-creation enjoyment were central-predictors within the networks. This study offers a comprehensive understanding of value co-creation and co-destruction between customers and technology actors, leading them to adopt and reject HSRs. Furthermore, it provides a pioneering methodological contribution to prescriptive network analytics that makes the network approach more accessible to academics and practitioners.
One strategy to program for generalization is to vary noncritical features in teaching exemplars, thereby avoiding noncritical features from being highly correlated with reinforcement and thus ...gaining faulty stimulus control. In the current translational evaluation, 2 groups of adults of typical development were taught to respond to arbitrary stimuli with experimenter‐defined critical and noncritical features in a matching‐to‐sample task. The teaching arrangement used for 1 group programmed for low correlation between noncritical features and reinforcement; the teaching arrangement used for the other group programmed for high correlation between noncritical features and reinforcement. Participants in the former group displayed (a) faster acquisition of matching, (b) less variability in correct responding, and (c) a decreased likelihood of faulty stimulus control developing during training. The results contribute towards advancing the study of stimulus control and developing an explicit technology of generalization to better serve consumers of the application of our science.
Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated ...myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies.