Regulatory B cells contribute to the regulation of immune responses in cancer, autoimmune disorders, allergic conditions and inflammatory diseases. Although most studies focus on regulatory B lymphocytes expressing interleukin‐10, there is growing evidence that B cells producing transforming growth factor β (TGF‐β) can also regulate T‐cell immunity in inflammatory diseases and promote the emergence of regulatory T cells that contribute…
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Depletion of architectural factors globally alters chromatin structure but only modestly affects gene expression. We revisit the structure-function relationship using the inactive X chromosome (Xi) as a model. We investigate cohesin imbalances by forcing its depletion or retention using degron-tagged RAD21 (cohesin subunit) or WAPL (cohesin release factor). Cohesin loss disrupts the Xi superstructure, unveiling superloops between escapee genes with minimal effect on gene repression. By contrast, forced cohesin…
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Dr. Kagan is interested in the ways that cells interact with each other and with the microbes they encounter; he is the Marian R. Neutra, PhD Professor of Pediatrics at Harvard Medical School and the Director of Basic Research and Shwachman Chair in Gastroenterology at Boston Children’s Hospital. Dr. Rotjan is a marine ecologist focused on corallivory (predation on live corals) and how corals respond to open wounds. She is also the co-chief scientist for the Phoenix Islands Protected Area (PIPA) in the Republic of Kiribati. Gauthier, the lead author of the study who is co-mentored by Kagan and Rotjan, has long-been interested in the immune systems of marine organisms and the microbes they interact with.
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The influence of genome organization on transcription is central to our understanding of cell type specification. Higher-order genome organization is established through short- and long-range DNA interactions. Coordination of these interactions, from single atoms to entire chromosomes, plays a fundamental role in transcriptional control of gene expression. Loss of this coupling can result in disease. Analysis of transcriptional regulation typically…
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Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic colonization. In the oral cavity, saliva containing the mucins MUC5B and MUC7 forms a pellicle that coats the soft tissue and teeth to prevent infection by oral pathogens, such as Streptococcus mutans. Salivary mucin can interact directly with microorganisms through selective agglutinin activity and bacterial binding, but the…
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Checkpoint Blockade Toxicities: Insights into Autoimmunity and Treatment

Checkpoint blockade has transformed not only the way cancers are treated, but also highlighted the importance of mounting a proper immune response against tumors. Despite advances in the field of immunotherapy, many patients develop a range of inflammatory toxicities that limit the efficacy of these therapies. These toxicities range from barrier site injury, such as colitis, to endocrine organ dysfunction,…
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The immune and enteric nervous (ENS) systems monitor the frontier with commensal and pathogenic microbes in the colon. The authors investigated whether FoxP3+ regulatory T (Treg) cells functionally interact with the ENS. Indeed, microbe-responsive RORγ+ and Helios+ subsets localized in close apposition to nitrergic and peptidergic nerve fibers in the colon lamina propria (LP). Enteric neurons inhibited in vitro Treg (iTreg) differentiation in a cell-contact-independent manner.…
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We present barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel insitu analyses (BOLORAMIS), a reverse transcription-free method for spatially-resolved, targeted, in situ RNA identification of single or multiple targets. BOLORAMIS was demonstrated on a range of cell types and human cerebral organoids. Singleplex experiments to detect coding and non-coding RNAs in human iPSCs showed a stem-cell signature pattern.…
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Current technologies and available scaffold materials do not support long-term cell viability, differentiation and maintenance of podocytes, the ultra-specialized kidney resident cells that are responsible for the filtration of the blood. We developed a new platform which imitates the native kidney microenvironment by decellularizing fibroblasts grown on surfaces with macromolecular crowding. Human immortalized podocytes cultured on this platform displayed superior…
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Ciliary neurotrophic factor (CNTF) is a leading therapeutic candidate for several ocular diseases and induces optic nerve regeneration in animal models. Paradoxically, however, although CNTF gene therapy promotes extensive regeneration, recombinant CNTF (rCNTF) has little effect. Because intraocular viral vectors induce inflammation, and because CNTF is an immune modulator, we investigated whether CNTF gene therapy acts indirectly through other immune…
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