To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use was of great interest.
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Liu, S., Liu, D., Shen, R., Li, D., Hu, Q., Yan, Y., Sun, J., Zhang, F., Wan, H., Dong, P., Feng, J., Zhang, R., Li, J., Zhang, L., & Tao, W. (2021). Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis. Scientific Reports, 11(1), 9132. https://doi.org/10.1038/s41598-021-88492-1 Cite
Investigators report that long-term stress surprisingly abrogates both T helper 1 (TH1)- and TH2-type responses orchestrated by invariant natural killer T cells.
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Rudak, P. T., Choi, J., Parkins, K. M., Summers, K. L., Jackson, D. N., Foster, P. J., Skaro, A. I., Leslie, K., McAlister, V. C., Kuchroo, V. K., Inoue, W., Lantz, O., & Haeryfar, S. M. M. (2021). Chronic stress physically spares but functionally impairs innate-like invariant T cells. Cell Reports, 35(2). https://doi.org/10.1016/j.celrep.2021.108979 Cite
Researchers used an in vitro model of muscle cell ischemia in which primary human skeletal myoblasts were exposed to hypoxic conditions for 6 hours.
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El Baradie, K. B. Y., Khan, M. B., Mendhe, B., Waller, J., O’Brien, F., & Hamrick, M. W. (2021). The cyclophilin inhibitor NIM-811 increases muscle cell survival with hypoxia in vitro and improves gait performance following ischemia–reperfusion in vivo. Scientific Reports, 11(1), 6152. https://doi.org/10.1038/s41598-021-85753-x Cite
Scientists targeted the shared IL-12Rβ1/p40 interface to design a panel of IL-12 partial agonists that preserved interferon gamma (IFNγ) induction by CD8 + T cells but impaired cytokine production from natural killer (NK) cells in vitro.
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Glassman, C. R., Mathiharan, Y. K., Jude, K. M., Su, L., Panova, O., Lupardus, P. J., Spangler, J. B., Ely, L. K., Thomas, C., Skiniotis, G., & Garcia, K. C. (2021). Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells. Cell, 184(4), 983-999.e24. https://doi.org/10.1016/j.cell.2021.01.018 Cite
The authors discuss the pathogenetic role of various cytokines in Hidradenitis suppurativa and potential therapeutic targets attempted or currently under investigation for this debilitating disease.
[International Journal of Molecular Sciences]
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Scientists found that the expression of galectin-7 was reduced in the skin lesions of patients with psoriasis. IL-17A and TNF-α, two cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes and the immortalized human keratinocyte cell line HaCaT.
[Journal of Clinical Investigation]
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Chen, H.-L., Lo, C.-H., Huang, C.-C., Lu, M.-P., Hu, P.-Y., Chen, C.-S., Chueh, D.-Y., Chen, P., Lin, T.-N., Lo, Y.-H., Hsiao, Y.-P., Hsu, D. K., & Liu, F.-T. (2020). Galectin‐7 downregulation in lesional keratinocytes contributes to enhanced IL‐17A signaling and skin pathology in psoriasis. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI130740 Cite
Investigators review new insights regarding the pathogenesis of psoriasis, as it relates to dendritic cells, Langerhans cells, macrophages, the signal transducer and activator of transcription 3 pathway, and aryl hydrocarbon receptor in cutaneous vascular endothelial cells.
[International Journal of Molecular Sciences]
Investigators used conventional and novel sequential immunostaining and flow cytometry to scrutinize RA-responsive T-cells in tissues and blood of allogeneic hematopoietic stem-cell transplantation patients and characterized the impact of RA on human T-cell alloresponses.
The authors found that the Pellino ubiquitin E3 ligase is activated by innate pattern-recognition receptors, such as Toll-like receptors, and was highly upregulated in human psoriatic skin lesions and murine psoriasis-like models.
[Experimental and Molecular Medicine]
Investigators report here that IL-17A mRNA and protein were detectable in some human triple-negative breast cancer cell lines and further upregulated by IL-23 and LPS stimulation.
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Dawod, B., Liu, J., Gebremeskel, S., Yan, C., Sappong, A., Johnston, B., Hoskin, D. W., Marshall, J. S., & Wang, J. (2020). Myeloid-derived suppressor cell depletion therapy targets IL-17A-expressing mammary carcinomas. Scientific Reports, 10(1), 13343. https://doi.org/10.1038/s41598-020-70231-7 Cite
Investigators characterized a population of interleukin 17-producing γδ T cells that seeded the testis of naive C57BL/6 mice, expand at puberty and persisted throughout adulthood.
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Wilharm, A., Brigas, H. C., Sandrock, I., Ribeiro, M., Amado, T., Reinhardt, A., Demera, A., Hoenicke, L., Strowig, T., Carvalho, T., Prinz, I., & Ribot, J. C. (2020). Microbiota-dependent expansion of testicular IL-17-producing Vγ6 + γδ T cells upon puberty promotes local tissue immune surveillance. Mucosal Immunology, 1–11. https://doi.org/10.1038/s41385-020-0330-6 Cite