A Double-Edged Sword of Immuno-Microenvironment in Cardiac Homeostasis and Injury Repair

In adaptive immunity, effector T cells, especially Th17 cells, lead to the pathogenesis of cardiac fibrosis, including the distal fibrosis and scar formation. Cardiomyocytes protectors, Treg cells, inhibit reduce the inflammatory response, then directly trigger the regeneration of local progenitor cell via IL-10.
[Signal Transduction and Targeted Therapy]
Sun, K., Li, Y., & Jin, J. (2021). A double-edged sword of immuno-microenvironment in cardiac homeostasis and injury repair. Signal Transduction and Targeted Therapy, 6(1), 1–16. https://doi.org/10.1038/s41392-020-00455-6 Cite
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Imbalance of TGF-β1/BMP-7 Pathways Induced by M2-polarized Macrophages Promotes Hepatocellular Carcinoma Aggressiveness

Investigators found that the imbalance of TGF-β1/BMP-7 pathways was associated with aggressive pathological features and poor clinical outcomes in hepatocellular carcinoma.
[Molecular Therapy]
Ning, J., Ye, Y., Bu, D., Zhao, G., Song, T., Liu, P., Yu, W., Wang, H., Li, H., Ren, X., Ying, G., Zhao, Y., & Yu, J. (2021). Imbalance of TGF-β1/BMP-7 Pathways Induced by M2-polarized Macrophages Promotes Hepatocellular Carcinoma Aggressiveness. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2021.02.016 Cite
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Relaxin Gene Delivery Modulates Macrophages to Resolve Cancer Fibrosis and Synergizes with Immune Checkpoint Blockade Therapy

Scientists revealed previously unidentified insights into the modulation of macrophages to regulate tumor-associated fibrosis, providing a feasible strategy to reverse the immunosuppressive environment and improve the therapeutic outcome of checkpoint immunotherapies.
[Science Advances]
Zhou, X., Liu, Y., Hu, M., Wang, M., Liu, X., & Huang, L. (2021). Relaxin gene delivery modulates macrophages to resolve cancer fibrosis and synergizes with immune checkpoint blockade therapy. Science Advances, 7(8), eabb6596. https://doi.org/10.1126/sciadv.abb6596 Cite
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Selective Elimination of Immunosuppressive T Cells in Patients with Multiple Myeloma

SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7+CD8+ T cells exhibited decreased immunoreactivity towards the MART-1aa26–35*A27L antigen.
[Leukemia]
Awwad, M. H. S., Mahmoud, A., Bruns, H., Echchannaoui, H., Kriegsmann, K., Lutz, R., Raab, M. S., Bertsch, U., Munder, M., Jauch, A., Weisel, K., Maier, B., Weinhold, N., Salwender, H. J., Eckstein, V., Hänel, M., Fenk, R., Dürig, J., Brors, B., … Hundemer, M. (2021). Selective elimination of immunosuppressive T cells in patients with multiple myeloma. Leukemia, 1–14. https://doi.org/10.1038/s41375-021-01172-x Cite
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6His‐Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species

In cultured hepatic stellate cells, extracellular 6His‐tagged recombinant human cytoglobin was endocytosed and accumulated in endosomes via clathrin‐mediated pathway.
[Hepatology]
Dat, N. Q., Thuy, L. T. T., Hieu, V. N., Hai, H., Hoang, D. V., Hai, N. T. T., Thuy, T. T. V., Komiya, T., Rombouts, K., Dong, M. P., Hanh, N. V., Hoang, T. H., Sato‐Matsubara, M., Daikoku, A., Kadono, C., Oikawa, D., Yoshizato, K., Tokunaga, F., Pinzani, M., & Kawada, N. (n.d.). 6His-tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species. Hepatology, n/a(n/a). https://doi.org/https://doi.org/10.1002/hep.31752 Cite
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T Cell-Tropic HIV Efficiently Infects Alveolar Macrophages through Contact with Infected CD4+ T Cells

Scientists collected alveolar macrophages by bronchoscopy performed in HIV-infected, antiretroviral therapy-naive and uninfected subjects.
[Scientific Reports]
Schiff, A. E., Linder, A. H., Luhembo, S. N., Banning, S., Deymier, M. J., Diefenbach, T. J., Dickey, A. K., Tsibris, A. M., Balazs, A. B., Cho, J. L., Medoff, B. D., Walzl, G., Wilkinson, R. J., Burgers, W. A., Corleis, B., & Kwon, D. S. (2021). T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells. Scientific Reports, 11(1), 3890. https://doi.org/10.1038/s41598-021-82066-x Cite
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HIV Induces Airway Basal Progenitor Cells to Adopt an Inflammatory Phenotype

Researchers hypothesized that HIV induced the basal stem/progenitor cells to express inflammatory mediators that contributed to the pathogenesis of emphysema.
[Scientific Reports]
Chung, N. P. Y., Khan, K. M. F., Kaner, R. J., O’Beirne, S. L., & Crystal, R. G. (2021). HIV induces airway basal progenitor cells to adopt an inflammatory phenotype. Scientific Reports, 11(1), 3988. https://doi.org/10.1038/s41598-021-82143-1 Cite
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Immune Function in X-linked Retinoschisis (XLRS) Subjects in an AAV8-RS1 Phase I/IIa Gene Therapy Trial

Scientists explored systemic immune changes in 11 subjects with X-linked retinoschisis in a Phase I/IIa AAV8-RS1 gene therapy trial.
[Molecular Therapy]
Mishra, A., Vijaysarathy, C., Cukras, C. A., Wiley, H. E., Sen, H. N., Zeng, Y., Wei, L., & Sieving, P. A. (2021). Immune function in X-linked retinoschisis (XLRS) subjects in an AAV8-RS1 Phase I/IIa gene therapy trial. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2021.02.013 Cite
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Clinical Implications of Systemic and Local Immune Responses in Human Angiosarcoma

Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. The authors investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio as a marker of systemic immune response
[npj Precision Oncology]
Chan, J. Y., Tan, G. F., Yeong, J., Ong, C. W., Ng, D. Y. X., Lee, E., Koh, J., Ng, C. C.-Y., Lee, J. Y., Liu, W., Wong, R. X., Ong, C.-A. J., Farid, M., Teh, B. T., & Soo, K. C. (2021). Clinical implications of systemic and local immune responses in human angiosarcoma. Npj Precision Oncology, 5(1), 1–13. https://doi.org/10.1038/s41698-021-00150-x Cite
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Macrophage-Derived EDA-A2 Inhibits Intestinal Stem Cells by Targeting miR-494/EDA2R/β-Catenin Signaling in Mice

In colitis crypts, a notable cytokine–cytokine receptor, miR-494-3p-targeted EDA2R and the ligand EDA-A2, suppressed colonic stemness and epithelial repair by inhibiting β-catenin/c-Myc. In differentiated intestinal epithelial cells, miR-494-3p inhibited macrophage recruitment, M1 activation and EDA-A2 secretion by targeting IKKβ/NF-κB in colitis.
[Communications Biology]
Song, L., Chang, R., Sun, X., Lu, L., Gao, H., Lu, H., Lin, R., Xu, X., Liu, Z., & Zhan, L. (2021). Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494/EDA2R/β-catenin signaling in mice. Communications Biology, 4(1), 1–14. https://doi.org/10.1038/s42003-021-01730-0 Cite
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Improved Diabetic Wound Healing by Bovine Lactoferricin Is Associated with Relevant Changes in the Skin Immune Response and Microbiota

The wound healing potential of bovine lactoferricin was investigated using in vitro, ex vivo, and in vivo models. Cell migration and proliferation were tested on keratinocytes and on porcine ears.
[Molecular Therapy-Methods & Clinical Development]
Mouritzen, M. V., Petkovic, M., Qvist, K., Poulsen, S. S., Alarico, S., Leal, E. C., Dalgaard, L. T., Empadinhas, N., Carvalho, E., & Jenssen, H. (2021). Improved diabetic wound healing by bovine lactoferricin is associated with relevant changes in the skin immune response and microbiota. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2021.02.008 Cite
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