Allies in the epidermis
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Co-option and neofunctionalization of stomatal executors for defence against herbivores in Brassicales
Co-option of gene regulatory networks leads to the acquisition of new cell types and tissues. Stomata, valves formed by guard cells (GCs), are present in most land plants and regulate CO2 exchange. The transcription factor (TF) FAMA globally regulates GC differentiation. In the Brassicales, FAMA also promotes the development of idioblast myrosin cells (MCs), another type of specialized cell along the vasculature essential for Brassicales-specific chemical defences. Here we show that in Arabidopsis thaliana, FAMA directly induces the TF gene WASABI MAKER (WSB), which triggers MC differentiation. WSB and STOMATAL CARPENTER 1 (SCAP1, a stomatal lineage-specific direct FAMA target), synergistically promote GC differentiation. wsb mutants lacked MCs and the wsb scap1 double mutant lacked normal GCs. Evolutionary analyses revealed that WSB is conserved across stomatous angiosperms. We propose that the conserved and reduced transcriptional FAMA–WSB module was co-opted before evolving to induce MC differentiation.
The AhR-Ovol1-Id1 regulatory axis in keratinocytes promotes epidermal and immune homeostasis in atopic dermatitis-like skin inflammation
The skin is our outer permeability and immune defense barrier against myriad external assaults. Aryl hydrocarbon receptor (AhR) senses environmental factors and regulates barrier robustness and immune homeostasis. AhR agonists have been approved by the FDA for psoriasis treatment and are in clinical trials for the treatment of atopic dermatitis (AD), but the underlying mechanism of action remains poorly defined. Here, we report that OVOL1/Ovol1 is a conserved and direct transcriptional target of AhR in epidermal keratinocytes. We show that OVOL1/Ovol1 influences AhR-mediated regulation of keratinocyte gene expression and that OVOL1/Ovol1 ablation in keratinocytes impairs the barrier-promoting function of AhR, exacerbating AD-like inflammation. Mechanistically, we have identified Ovol1’s direct downstream targets genome-wide and provided in vivo evidence supporting the role of Id1 as a functional target in barrier maintenance, disease suppression, and neutrophil accumulation. Furthermore, our findings reveal that an IL-1/dermal γδT cell axis exacerbates type 2 and 3 immune responses downstream of barrier perturbation in Ovol1-deficient AD skin. Finally, we present data suggesting the clinical relevance of OVOL1 and ID1 functions in human AD skin. Our study highlights a keratinocyte-intrinsic AhR-Ovol1-Id1 regulatory axis that promotes both epidermal and immune homeostasis in the context of skin inflammation, identifying new therapeutic targets.
The apoplastic pH is a key determinant in the hypocotyl growth response to auxin dosage and light
Auxin is a core phytohormone regulating plant elongation growth. While auxin typically promotes hypocotyl elongation, excessive amounts of auxin inhibit elongation. Moreover, auxin usually promotes light-grown, but inhibits dark-grown hypocotyl elongation. How dosage and light condition change the plant’s response to auxin, also known as auxin’s biphasic effect or dual effect, has long been mysterious. Auxin induces cell expansion primarily through apoplastic acidification and the subsequent ‘acid growth’ mechanism. Here we show that this pathway operates for both stimulatory and inhibitory auxin doses and under both dark and light conditions. Regardless of the dosage, more auxin induces more transcripts of SAURs (Small Auxin-Up RNAs), leading to a stronger activation of plasma membrane H+-ATPases (AHAs) and progressive acidification of the apoplast in hypocotyl epidermis. Apoplastic acidification promotes growth but only above a certain pH threshold, below which excessive acidification inhibits elongation. Auxin overdosage-triggered hypocotyl inhibition can be alleviated by suppressing the AHA activity or raising the apoplastic pH. Light-grown hypocotyls exhibit a higher apoplastic pH, which impedes cell elongation and counteracts auxin-induced over-acidification. Auxin and light antagonistically regulate the SAUR-PP2C.D-AHA pathway in the hypocotyl and influence plant elongation growth. Our findings suggest that the biphasic effect of auxin results from the biphasic response of hypocotyl cells to decreasing apoplastic pH.
Type 2 immunity in allergic diseases
Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.
3D printable and myoelectrically sensitive hydrogel for smart prosthetic hand control
Surface electromyogram (sEMG) serves as a means to discern human movement intentions, achieved by applying epidermal electrodes to specific body regions. However, it is difficult to obtain high-fidelity sEMG recordings in areas with intricate curved surfaces, such as the body, because regular sEMG electrodes have stiff structures. In this study, we developed myoelectrically sensitive hydrogels via 3D printing and integrated them into a stretchable, flexible, and high-density sEMG electrodes array. This electrode array offered a series of excellent human-machine interface (HMI) features, including conformal adherence to the skin, high electron-to-ion conductivity (and thus lower contact impedance), and sustained stability over extended periods. These attributes render our electrodes more conducive than commercial electrodes for long-term wearing and high-fidelity sEMG recording at complicated skin interfaces. Systematic in vivo studies were used to investigate its efficacy to control a prosthetic hand by decoding sEMG signals from the human hand via a multiple-channel readout circuit and a sophisticated artificial intelligence algorithm. Our findings demonstrate that the 3D printed gel myoelectric sensing system enables real-time and highly precise control of a prosthetic hand.
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