Inadequate data sharing hampers research

        In an analysis of 3,556 biomedical and health science articles published in 282 journals by BMC, researchers from the Catholic University of Croatia in Zagreb found that >90% of 1,792 authors who had stated that their data sets would be available on reasonable request either failed to respond to or declined the requests for data sharing. A mere 6.7% of these authors shared the requested data in a usable form. Reasons cited for the inability to share data included privacy concerns, participant confidentiality, misplaced data, concern for use in misleading secondary analysis, and language barriers. To tackle the problem, it has been suggested that journals require authors to detail where and how they will share data and that funders require grant applicants to prepare a statement of data management and sharing. (Nature 606:853, 2022. Editorial note: JID expects large datasets to be made available to reviewers upon submission; further, such datasets must be deposited in recognized public repositories and made fully accessible at the time of online publication. Selected by E. Tschachler

        SC7A11 dampens efferocytosis by dendritic cells during wound healing

        Apoptotic cells are removed by phagocytes through efferocytosis, and defects in this process lead to nonresolving inflammation and dysregulated tissue repair, such as in nonhealing wounds in diabetes. Maschalidi et al. (2022) identified significant alterations in the expression levels of solute carrier family genes in efferocytotic dendritic cells, with the largest increase in Slc7a11. Additional investigation revealed that SLC7A111 functions as a negative regulator of dendritic cell efferocytosis. Accordingly, blockade of SLC7A11 with the inhibitor erastin concomitant with the administration of apoptotic cells at wound sites dramatically increased efferocytosis and accelerated wound healing in both wild-type and diabetes-prone mice. Molecularly, the TGFβ family member GDF15, secreted by efferocytotic dendritic cells, acted as a key mediator to facilitate wound healing downstream of SLC7A11. These studies suggest that inhibition of SLC7A11 may be an effective means to improve efferocytosis by dendritic cells and consequently facilitate cutaneous wound healing, especially in patients with diabetes. (Nature 606:776‒84, 2022. Selected by L. Eckhart

        The mechanically activated ion channel PIEZO1 plays a role in itch sensation

        Somatosensory neurons with chemosensory receptors are known to drive itch behaviors in mice; however, the molecular underpinnings of mechanical itch in the periphery remain unclear. Hill et al. (2022) discovered that the mechanically activated ion channel PIEZO1 is expressed in NPPB+ dorsal root ganglia neurons and is the primary mediator for mechanically activated currents in somatostatin (SST)-positive dorsal root ganglia neurons. Through the examination of multiple different itch inducers (histamine, IL-31, and chloroquine), these studies showed that PIEZO1 transduces mechanical itch and alloknesis through SST+NPPB+ itch receptors. Loss of PIEZO1 function led to a dramatic decrease in mechanically evoked scratching behavior and in itch-evoked sensitization in both acute and chronic itch models. In a PIEZO1 gain-of-function mouse model, increased PIEZO1 activity exacerbated mechanical itch. Together, these findings describe a subset of itch-sensing neurons that respond to both chemical and mechanical pruritogens, highlight a role for PIEZO1 in the transduction of mechanical itch, and suggest that antagonists of this ion channel may be efficacious for treating itch. (Nature 607:104‒10, 2022. Selected by J. Gelfand

        IL-17A‒HIF1α axis drives glycolysis and epithelial healing

        Hypoxia-induced factors (HIFs) mediate cellular adaptation to the hypoxic wound environment during wound healing, but the role of immune cells in this environment during tissue repair remains enigmatic. Konieczny et al. (2022) found that RORγt+ γδ T cells produced IL-17A, which induced epithelial migration at the wound edge. This γδ T cell‒derived IL-17A is necessary and sufficient for HIF1α activation at the wound edge through the upstream factors extracellular signal‒regulated kinase, protein kinase B, and mTOR. Under conditions of acute hypoxia, epithelial HIF1α was activated, and this phenomenon was enhanced in the presence of IL-17A. However, under conditions of chronic hypoxia, loss of HIF1α and mTOR signaling was observed, and this loss could be abrogated by treatment with IL-17A. The IL-17A‒HIF1α axis directs a program of glycolysis to fuel migration at the wound edge, and interference with this process inhibited wound re-epithelialization. Thus, IL-17A serves as a second signal for re-epithelialization during wound healing in addition to cell-autonomous oxygen monitoring, and modulation of the IL-17A‒HIF1α axis may be beneficial in a variety of epithelial inflammatory diseases and cancer. (Science 377:eabg9302, 2022. Selected by N. Ward and M. Tomic-Canic

        Asynthetic fission of skin cells increases surface area in zebrafish

        Zebrafish offer an excellent opportunity to visualize skin cell behavior in a living animal with high resolution. Chan et al. (2022) developed a multicolor cell membrane tagging system to capture changes in cell size and shape during zebrafish larval development. Monitoring of superficial epithelial cells (SECs) showed that one SEC can divide to yield up to four progeny cells during a period of massive division to maintain whole-body coverage. These SECs proliferated through a distinct mode of cell division, asynthetic fission, that requires minimal-to-no DNA synthesis. As many as half of these progeny cells exhibited reduced genome size. On the basis of these observations, asynthetic fission appears to be a frugal and error-prone yet highly efficient means to produce sufficient epithelial coverage during a rapid growth phase of the fish. Future studies are needed to examine whether defects in asynthetic fission lead to faulty skin barrier function and whether these processes may be conserved in mammals as well. (Nature 605:119‒25, 2022. Selected by M. Tomic-Canic and A. Di Nardo