Researchers analyzed the molecular determinants of monocytic and macrophagic commitment by profiling the EGR1 transcription factor. EGR1 is essential for monopoiesis and binds enhancers that regulate monocytic developmental genes such as CSF1R.
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Scientists compared African green monkeys inoculated with infectious SARS-CoV-2 or irradiated, inactivated virus to study the dynamics of virus replication throughout the respiratory tract. Interestingly, genomic RNA from the animals inoculated with the irradiated virus was found to be highly stable, whereas sub-genomic RNA, an indicator of viral replication, was found to degrade quickly.
[Science Translational Medicine]
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Speranza, E., Williamson, B. N., Feldmann, F., Sturdevant, G. L., Pérez, L. P., Meade-White, K., Smith, B. J., Lovaglio, J., Martens, C., Munster, V. J., Okumura, A., Shaia, C., Feldmann, H., Best, S. M., & Wit, E. de. (2021). Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.abe8146 Cite
During synovial tissue homeostasis, both monocyte-derived F4/80int and self-renewing F4/80hi tissue–resident, macrophage populations were identified.
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Huang, Q.-Q., Doyle, R., Chen, S.-Y., Sheng, Q., Misharin, A. V., Mao, Q., Winter, D. R., & Pope, R. M. (2021). Critical role of synovial tissue–resident macrophage niche in joint homeostasis and suppression of chronic inflammation. Science Advances, 7(2), eabd0515. https://doi.org/10.1126/sciadv.abd0515 Cite
Scientists found that CCR2highCX3CR1low monocytes recruited to the injured brain were cytokine-dependently converted into CCR2lowCX3CR1high macrophages, especially under the influence of IL-4 and IL-13, thereby attenuating the neuroinflammation following sterile ischemic stroke.
[Translational Stroke Research]
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Park, J., Kim, J. Y., Kim, Y. R., Huang, M., Chang, J. Y., Sim, A. Y., Jung, H., Lee, W. T., Hyun, Y.-M., & Lee, J. E. (2021). Reparative System Arising from CCR2(+) Monocyte Conversion Attenuates Neuroinflammation Following Ischemic Stroke. Translational Stroke Research. https://doi.org/10.1007/s12975-020-00878-x Cite
Atherosclerosis was studied in the ascending aortic arch and compared to mice without bone marrow transplantation (BMT). In BMT mice neutral lipid and myeloid cell topography were lower in lesions after feeding a cholesterol-rich diet for three, six and 12 weeks.
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Ikeda Jiro, Scipione Corey A, Hyduk Sharon, Althagafi Marwan G, Atif Jawairia, Dick Sarah A, Rajora Maneesha A, Jang Erika, Emoto Takuo, Murakami Junichi, Ikeda Noriko, Ibrahim Hisham M, Polenz Chanele K, Gao Xiaotang, Tai Kelly, Jongstra-Bilen Jenny, Nakashima Ryota, Epelman Slava, Robbins Clinton, … Cybulsky Myron I. (n.d.). Radiation Impacts Early Atherosclerosis by Suppressing Intimal LDL Accumulation. Circulation Research, 0(0). https://doi.org/10.1161/CIRCRESAHA.119.316539 Cite
Researchers report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Patients with liver metastases derive limited benefit from immunotherapy independent of other established biomarkers of response.
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Yu, J., Green, M. D., Li, S., Sun, Y., Journey, S. N., Choi, J. E., Rizvi, S. M., Qin, A., Waninger, J. J., Lang, X., Chopra, Z., El Naqa, I., Zhou, J., Bian, Y., Jiang, L., Tezel, A., Skvarce, J., Achar, R. K., Sitto, M., … Zou, W. (2021). Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nature Medicine, 1–13. https://doi.org/10.1038/s41591-020-1131-x Cite
Scientists report a key β cell-macrophage crosstalk pathway mediated by the miRNA-29-TNF-receptor-associated factor 3 (TRAF3) axis.
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Sun, Y., Zhou, Y., Shi, Y., Zhang, Y., Liu, K., Liang, R., Sun, P., Chang, X., Tang, W., Zhang, Y., Li, J., Wang, S., Zhu, Y., & Han, X. (2021). Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3. Cell Reports, 34(1). https://doi.org/10.1016/j.celrep.2020.108576 Cite
The authors found impaired Kupffer cell bacterial clearance and systemic bacterial dissemination in mice with liver injury. Increased PD-1 and PD-L1 expression was detected in Kupffer cells and lymphocyte subsets, respectively, during resolution of injury.
[European Journal of Clinical Investigation]
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Triantafyllou, E., Gudd, C. L. C., Mawhin, M.-A., Husbyn, H. C., Trovato, F. M., Siggins, M. K., O’Connor, T., Kudo, H., Mukherjee, S. K., Wendon, J. A., Bernsmeier, C., Goldin, R. D., Botto, M., Khamri, W., McPhail, M. J. W., Possamai, L. A., Woollard, K. J., Antoniades, C. G., & Thursz, M. R. (2020). PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI140196 Cite
Researchers hypothesized that obstructive sleep apnea syndrome (OSA) children’s serum can activate NFκB in cardiomyocytes (CM) and effect their viability. In order to explore the role played by NFκB in OSA cardiovascular pathophysiology, rat, mouse and human immortalized CM were exposed to human serum drawn from OSA children and matched controls.
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Researchers demonstrated that regulatory T cell ablation-dependent anti-tumor effects in murine breast cancer required intratumoral recruitment of CCR2+ inflammatory monocytes, which primarily differentiated into tumor-associated macrophages, and led to reprogramming of their function in an IFN-γ-dependent manner.
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Clark, N. M., Martinez, L. M., Murdock, S., deLigio, J. T., Olex, A. L., Effi, C., Dozmorov, M. G., & Bos, P. D. (2020). Regulatory T Cells Support Breast Cancer Progression by Opposing IFN-γ-Dependent Functional Reprogramming of Myeloid Cells. Cell Reports, 33(10). https://doi.org/10.1016/j.celrep.2020.108482 Cite
Mechanistic studies revealed roles of eosinophil IL4 and cationic protein mEar1 in blocking H2O2– and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer.
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