Does the Epithelial Barrier Hypothesis Explain the Increase in Allergy, Autoimmunity and Other Chronic Conditions?

Scientists discuss how the immune responses to dysbiotic microbiota that cross the damaged barrier may be involved in the development of allergic and autoimmune diseases.
[Nature Reviews Immunology]
Akdis, C. A. (2021). Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nature Reviews Immunology, 1–13. https://doi.org/10.1038/s41577-021-00538-7 Cite
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Gene Expression Profiling of Brain Endothelial Cells after Experimental Subarachnoid Hemorrhage

Investigators used gene expression profiling to identify 707 unique genes that were significantly differentially expressed in mouse brain endothelial cells after subarachnoid hemorrhage.
[Scientific Reports]
Tso, M. K., Turgeon, P., Bosche, B., Lee, C. K., Nie, T., D’Abbondanza, J., Ai, J., Marsden, P. A., & Macdonald, R. L. (2021). Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage. Scientific Reports, 11(1), 7818. https://doi.org/10.1038/s41598-021-87301-z Cite
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Neural Stem Cells Traffic Functional Mitochondria via Extracellular Vesicles

The authors investigated the hypothesis that neural stem cells release and traffic functional mitochondria via extracellular vesicles to restore mitochondrial function in target cells.
[PLoS Biology]
Peruzzotti-Jametti, L., Bernstock, J. D., Willis, C. M., Manferrari, G., Rogall, R., Fernandez-Vizarra, E., Williamson, J. C., Braga, A., Bosch, A. van den, Leonardi, T., Krzak, G., Kittel, Á., Benincá, C., Vicario, N., Tan, S., Bastos, C., Bicci, I., Iraci, N., Smith, J. A., … Pluchino, S. (2021). Neural stem cells traffic functional mitochondria via extracellular vesicles. PLOS Biology, 19(4), e3001166. https://doi.org/10.1371/journal.pbio.3001166 Cite
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Sorrento Enters Into Merger Agreement to Acquire Late-Stage Oncology Company ACEA Therapeutics

Sorrento Therapeutics, Inc. announced the signing of a merger agreement pursuant to which Sorrento will acquire ACEA Therapeutics, Inc. The acquisition will include late clinical stage drug Abivertinib, clinical stage candidate AC0058, preclinical stage candidate AC0939, and ACEA’s extensive proprietary library of small molecules, which potentially have applications for numerous human disease indications, including non-small cell lung cancer, B cell lymphomas, systemic lupus, rheumatoid arthritis, multiple sclerosis and viral infections.
[Sorrento Therapeutics, Inc. (Globe Newswire, Inc.)]
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BrainStorm Announces Positive Topline Data in Phase II Study Evaluating NurOwn® as a Treatment for Progressive MS

BrainStorm Cell Therapeutics Inc. announced topline data from the company’s Phase II trial evaluating three repeated administrations of NurOwn®, each given two months apart, as a treatment for progressive multiple sclerosis (MS).
[BrainStorm Cell Therapeutics Inc.]
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Genmab Announces European Marketing Authorization for Kesimpta® (Ofatumumab) in Relapsing Multiple Sclerosis

Genmab A/S announced that the European Commission has granted Novartis marketing authorization for the use of Kesimpta® in the treatment of relapsing forms of multiple sclerosis in adults with active disease defined by clinical or imaging features.
[Genmab A/S]
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Overcoming the Inhibitory Microenvironment Surrounding Oligodendrocyte Progenitor Cells Following Experimental Demyelination

The authors identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans.
[Nature Communications]
Saraswat, D., Shayya, H. J., Polanco, J. J., Tripathi, A., Welliver, R. R., Pol, S. U., Seidman, R. A., Broome, J. E., O’Bara, M. A., van Kuppervelt, T. H., Phillips, J. J., Dutta, R., & Sim, F. J. (2021). Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination. Nature Communications, 12(1), 1923. https://doi.org/10.1038/s41467-021-22263-4 Cite
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The Survival and Function of IL-10-Producing Regulatory B Cells Are Negatively Controlled by SLAMF5

The authors identified SLAMF5 for controlling IL-10+ regulatory B cell (Breg) maintenance and function. In EAE, the deficiency of SLAMF5 in B cells causes accumulation of IL10+ Bregs in the central nervous system and periphery.
[Nature Communications]
Radomir, L., Kramer, M. P., Perpinial, M., Schottlender, N., Rabani, S., David, K., Wiener, A., Lewinsky, H., Becker-Herman, S., Aharoni, R., Milo, R., Mauri, C., & Shachar, I. (2021). The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5. Nature Communications, 12(1), 1893. https://doi.org/10.1038/s41467-021-22230-z Cite
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Mesenchymal Stem/Stromal Cells as a Valuable Source for the Treatment of Immune-Mediated Disorders

The authors discuss the therapeutic applications of mesenchymal stem/stromal cell (MSC) secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs are discussed.
[Stem Cell Research & Therapy]
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Involvement of Cytotoxic Eomes-Expressing CD4+ T Cells in Secondary Progressive Multiple Sclerosis

Few Eomes+ Th cells circulate in RRMS patient peripheral blood, primary progressive MS patients, or healthy controls, but Eomes+ Th cells were significantly increased in SPMS.
[Proceedings of the National Academy of Sciences of the United States of America]
Raveney, B. J. E., Sato, W., Takewaki, D., Zhang, C., Kanazawa, T., Lin, Y., Okamoto, T., Araki, M., Kimura, Y., Sato, N., Sano, T., Saito, Y., Oki, S., & Yamamura, T. (2021). Involvement of cytotoxic Eomes-expressing CD4+ T cells in secondary progressive multiple sclerosis. Proceedings of the National Academy of Sciences, 118(11). https://doi.org/10.1073/pnas.2021818118 Cite
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The Hedgehog Pathway Suppresses Neuropathogenesis in CD4 T Cell-Driven Inflammation

Researchers showed that the CNS-endogenous hedgehog pathway attenuated the pathogenicity of human and mouse effector CD4 T cells by regulating their production of inflammatory cytokines.
[Brain]
Benallegue, N., Kebir, H., Kapoor, R., Crockett, A., Li, C., Cheslow, L., Abdel-Hakeem, M. S., Gesualdi, J., Miller, M. C., Wherry, E. J., Church, M. E., Blanco, M. A., & Alvarez, J. I. (2021). The hedgehog pathway suppresses neuropathogenesis in CD4 T cell-driven inflammation. Brain, awab083. https://doi.org/10.1093/brain/awab083 Cite
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