47 research outputs found

    Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium

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    The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we showed that emergence of the first cohorts of Aire(+) mTECs at this key developmental stage, prior to αβ T cell repertoire selection, was jointly directed by Rankl(+) lymphoid tissue inducer cells and invariant Vγ5(+) dendritic epidermal T cell (DETC) progenitors that are the first thymocytes to express the products of gene rearrangement. In turn, generation of Aire(+) mTECs then fostered Skint-1-dependent, but Aire-independent, DETC progenitor maturation and the emergence of an invariant DETC repertoire. Hence, our data attributed a functional importance to the temporal development of Vγ5(+) γδ T cells during thymus medulla formation for αβ T cell tolerance induction and demonstrated a Rank-mediated reciprocal link between DETC and Aire(+) mTEC maturation

    Comparative Analysis of ActiGraph Step Counting Methods in Adults: A Systematic Literature Review and Meta-Analysis

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    PURPOSE: The primary aim of this study was to compare steps/day across ActiGraph models, wear locations, and filtering methods. A secondary aim was to compare ActiGraph steps/day to those estimated by the ankle-worn StepWatch. METHODS: We conducted a systematic literature review to identify studies of adults published before May 12, 2022, that compared free-living steps/day of ActiGraph step-counting methods and studies that compared ActiGraph to StepWatch. Random effects meta-analysis compared ActiGraph models, wear locations, filter mechanisms, and ActiGraph to StepWatch steps/day. A sensitivity analysis of wear location by younger and older age was included. RESULTS: Twelve studies, with 46 comparisons, were identified. When worn on the hip, the AM-7164 recorded 123% of the GT series steps (no low-frequency extension (no LFE) or default filter). However, the AM-7164 recorded 72% of the GT series steps when the LFE was enabled. Independent of the filter used (i.e., LFE, no LFE), ActiGraph GT series monitors captured more steps on the wrist than on the hip, especially among older adults. Enabling the LFE on the GT series monitors consistently recorded more steps, regardless of wear location. When using the default filter (no LFE), ActiGraph recorded fewer steps than StepWatch (ActiGraph on hip 73% and ActiGraph on wrist 97% of StepWatch steps). When LFE was enabled, ActiGraph recorded more steps than StepWatch (ActiGraph on the hip 132% and ActiGraph on the wrist 178% of StepWatch steps). CONCLUSIONS: The choice of ActiGraph model, wear location, and filter all impacted steps/day in adults. These can markedly alter the steps recorded compared to a criterion method (StepWatch). This review provides critical insights for comparing studies using different ActiGraph step-counting methods

    Innate Lymphoid Cells: 10 Years On

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    International audienceInnate lymphoid cells (ILCs) are lymphocytes that do not express the type of diversified antigen receptors expressed on T cells and B cells. ILCs are largely tissue-resident cells and are deeply integrated into the fabric of tissues. The discovery and investigation of ILCs over the past decade has changed our perception of immune regulation and how the immune system contributes to the maintenance of tissue homeostasis. We now know that cytokine-producing ILCs contribute to multiple immune pathways by, for example, sustaining appropriate immune responses to commensals and pathogens at mucosal barriers, potentiating adaptive immunity, and regulating tissue inflammation. Critically, the biology of ILCs also extends beyond classical immunology to metabolic homeostasis, tissue remodeling, and dialog with the nervous system. The last 10 years have also contributed to our greater understanding of the transcriptional networks that regulate lymphocyte commitment and delineation. This, in conjunction with the recent advances in our understanding of the influence of local tissue microenvironments on the plasticity and function of ILCs, has led to a re-evaluation of their existing categorization. In this review, we distill the advances in ILC biology over the past decade to refine the nomenclature of ILCs and highlight the importance of ILCs in tissue homeostasis, morphogenesis, metabolism, repair, and regeneration

    Activation of neutrophils by autocrine IL-17A–IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2

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    Here we identified a population of bone marrow neutrophils that constitutively expressed the transcription factor RORγt and produced and responded to interleukin 17A (IL-17A (IL-17)). IL-6, IL-23 and RORγt, but not T cells or natural killer (NK) cells, were required for IL-17 production in neutrophils. IL-6 and IL-23 induced expression of the receptors IL-17RC and dectin-2 on neutrophils, and IL-17RC expression was augmented by activation of dectin-2. Autocrine activity of IL-17A and its receptor induced the production of reactive oxygen species (ROS), and increased fungal killing in vitro and in a model of Aspergillus-induced keratitis. Human neutrophils also expressed RORγt and induced the expression of IL-17A, IL-17RC and dectin-2 following stimulation with IL-6 and IL-23. Our findings identify a population of human and mouse neutrophils with autocrine IL-17 activity that probably contribute to the etiology of microbial and inflammatory diseases
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