Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity

The mechanisms by which regulatory T (Treg) cells differentially control allergic and autoimmune responses remain unclear. Researchers showed that Treg cells in food allergy had decreased expression of transforming growth factor beta 1 (TGF-β1) because of interleukin-4- and signal transducer and activator of transciription-6-dependent inhibition of Tgfb1 transcription.
[Immunity]
Turner, J. A., Stephen-Victor, E., Wang, S., Rivas, M. N., Abdel-Gadir, A., Harb, H., Cui, Y., Fanny, M., Charbonnier, L.-M., Fong, J. J. H., Benamar, M., Wang, L., Burton, O. T., Bansal, K., Bry, L., Zhu, C., Li, Q.-Z., Clement, R. L., Oettgen, H. C., … Chatila, T. A. (2020). Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.10.002 Cite
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Biodiversity Intervention Enhances Immune Regulation and Health-Associated Commensal Microbiota among Daycare Children

Scientists conducted the first human intervention trial in which urban environmental biodiversity was manipulated to examine its effects on the commensal microbiome and immunoregulation in children.
[Science Advances]
Roslund, M. I., Puhakka, R., Grönroos, M., Nurminen, N., Oikarinen, S., Gazali, A. M., Cinek, O., Kramná, L., Siter, N., Vari, H. K., Soininen, L., Parajuli, A., Rajaniemi, J., Kinnunen, T., Laitinen, O. H., Hyöty, H., Sinkkonen, A., & Group, A. research. (2020). Biodiversity intervention enhances immune regulation and health-associated commensal microbiota among daycare children. Science Advances, 6(42), eaba2578. https://doi.org/10.1126/sciadv.aba2578 Cite
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Formaldehyde Exposure Induces Regulatory T Cell-Mediated Immunosuppression via Calcineurin-NFAT Signalling Pathway

Researchers investigated the effects of Formaldehyde exposure on splenic immune responses wherein helper T cells become activated and differentiate into effector T and regulatory T cells.
[Scientific Reports]
Formaldehyde exposure induces regulatory T cell-mediated immunosuppression via calcineurin-NFAT signalling pathway | Scientific Reports. (n.d.). Retrieved October 13, 2020, from https://www.nature.com/articles/s41598-020-72502-9 Cite
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IL-10 Producing Type 2 Innate Lymphoid Cells Prolong Islet Allograft Survival

Scientist showed that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells.
[EMBO Molecular Medicine]
Huang, Q., Ma, X., Wang, Y., Niu, Z., Wang, R., Yang, F., Wu, M., Liang, G., Rong, P., Wang, H., Harris, D. C., Wang, W., & Cao, Q. (2020). IL-10 producing type 2 innate lymphoid cells prolong islet allograft survival. EMBO Molecular Medicine, n/a(n/a), e12305. https://doi.org/10.15252/emmm.202012305 Cite
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Single-Cell RNA Sequencing Highlights the Role of Inflammatory Cancer-Associated Fibroblasts in Bladder Urothelial Carcinoma

Scientists found that tumor cells down regulated MHC-II molecules, suggesting that the downregulated immunogenicity of cancer cells may contribute to the formation of an immunosuppressive microenvironment.
[Nature Communications]
Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma | Nature Communications. (n.d.). Retrieved October 9, 2020, from https://www.nature.com/articles/s41467-020-18916-5 Cite
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Cellular Immunotherapies in Pre-Clinical Large Animal Models of Transplantation

Investigators highlight the contributions of large animal models to the development and fine-tuning of hematopoietic cell transplant and additional cellular therapies to improve organ transplantation outcomes.
[Biology of Blood and Marrow Transplantation]
Matar, A. J., Crepeau, R. L., & Duran-Struuck, R. (2020). Cellular Immunotherapies in Pre-Clinical Large Animal Models of Transplantation. Biology of Blood and Marrow Transplantation, 0(0). https://doi.org/10.1016/j.bbmt.2020.09.032 Cite
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Immune Remodeling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection

Extracellular matrix-rich tumors exhibited a stem cell-like gene expression profile and superior tumor-initiating capacity, whereas such features were absent in responder tumors.
[Cancer Immunology Research]
Pires, A., Greenshields-Watson, A., Jones, E., Smart, K., Lauder, S. N., Somerville, M., Milutinovic, S., Kendrick, H., Hindley, J. P., French, R., Smalley, M. J., Watkins, W. J., Andrews, R., Godkin, A., & Gallimore, A. (2020). Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0070 Cite
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Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection

Scientists defined an extended role for an effective immune response, not just in direct killing of tumor cells, but in widescale remodelling of the tumor microenvironment to favor loss of ECM, elimination of cancer stem cells, and propagation of adaptive immunity.
[Cancer Immunology Research]
Pires, A., Greenshields-Watson, A., Jones, E., Smart, K., Lauder, S. N., Somerville, M., Milutinovic, S., Kendrick, H., Hindley, J. P., French, R., Smalley, M. J., Watkins, W. J., Andrews, R., Godkin, A., & Gallimore, A. (2020). Immune Remodelling of the Extracellular Matrix Drives Loss of Cancer Stem Cells and Tumor Rejection. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0070 Cite
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HIF-2α Is Indispensable for Regulatory T Cell Function

Researchers showed that Treg cell development was normal in mice with Foxp3-specific knockout of hypoxia-inducible factor 1α (HIF-1α) or HIF-2α.
[Nature Communications]
Hsu, T.-S., Lin, Y.-L., Wang, Y.-A., Mo, S.-T., Chi, P.-Y., Lai, A. C.-Y., Pan, H.-Y., Chang, Y.-J., & Lai, M.-Z. (2020). HIF-2α is indispensable for regulatory T cell function. Nature Communications, 11(1), 5005. https://doi.org/10.1038/s41467-020-18731-y Cite
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Repurposing a Novel Anti-Cancer RXR Agonist to Attenuate Acute GVHD and Maintain Graft-Versus-Leukemia Responses

The authors showed that in vivo IRX4204 was compared favorably with FK506 in abrogating acute graft-versus-host disease, which was associated with inhibiting allogeneic donor T cell proliferation, reducing T helper 1 differentiation and promoting regulatory T cell generation.
[Blood]
Thangavelu, G., Wang, C., Loschi, M., Saha, A., Osborn, M., Furlan, S. N., Aoyama, K., McDonald-Hyman, C., Aguilar, E. G., Janesick, A. S., Chandraratna, R. A., Refaeli, Y., Panoskaltsis-Mortari, A., MacDonald, K. P., Hill, G. R., Zeiser, R., Maillard, I., Serody, J., Murphy, W. J., … Blazar, B. R. (n.d.). Repurposing a novel anti-cancer RXR agonist to attenuate acute GVHD and maintain graft-versus-leukemia responses. Blood. https://doi.org/10.1182/blood.2020005628 Cite
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An Antibody Targeting ICOS Increases Intratumoral Cytotoxic to Regulatory T Cell Ratio and Induces Tumor Regression

Researchers performed immune profiling of samples from tumor bearing mice and cancer patients to demonstrate differential expression of ICOS in immune T cell subsets in different tissues. ICOS expression was higher on intratumoral TReg than on effector CD8 T cells.
[Cancer Immunology Research]
Sainson, R. C. A., Thotakura, A. K., Kosmac, M., Borhis, G., Parveen, N., Kimber, R., Carvalho, J., Henderson, S. J., Pryke, K. L., Okell, T., O’Leary, S., Ball, S., Krinks, C. V., Gamand, L., Taggart, E., Pring, E. J., Ali, H., Craig, H., Wong, V. W. Y., … McCourt, M. (2020). An antibody targeting ICOS increases intratumoral cytotoxic to regulatory T cell ratio and induces tumor regression. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0034 Cite
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