Discovery of a Novel RORγ Antagonist with Skin-Restricted Exposure for Topical Treatment of Mild to Moderate Psoriasis

To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use was of great interest.
[Scientific Reports]
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
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Chronic Stress Physically Spares but Functionally Impairs Innate-Like Invariant T Cells

Investigators report that long-term stress surprisingly abrogates both T helper 1 (TH1)- and TH2-type responses orchestrated by invariant natural killer T cells.
[Cell Reports]
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
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The Cyclophilin Inhibitor NIM-811 Increases Muscle Cell Survival with Hypoxia In Vitro and Improves Gait Performance Following Ischemia–Reperfusion In Vivo

Researchers used an in vitro model of muscle cell ischemia in which primary human skeletal myoblasts were exposed to hypoxic conditions for 6 hours.
[Scientific Reports]
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
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Structural Basis for IL-12 and IL-23 Receptor Sharing Reveals a Gateway for Shaping Actions on T versus NK Cells

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.
[Cell]
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
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Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa

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]
Del Duca, E., Morelli, P., Bennardo, L., Di Raimondo, C., & Nisticò, S. P. (2020). Cytokine Pathways and Investigational Target Therapies in Hidradenitis Suppurativa. International Journal of Molecular Sciences, 21(22), 8436. https://doi.org/10.3390/ijms21228436 Cite
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Galectin-7 Downregulation in Lesional Keratinocytes Contributes to Enhanced IL-17A Signaling and Skin Pathology in Psoriasis

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]
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
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New Treatment Addressing the Pathogenesis of Psoriasis

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]
Tokuyama, M., & Mabuchi, T. (2020). New Treatment Addressing the Pathogenesis of Psoriasis. International Journal of Molecular Sciences, 21(20), 7488. https://doi.org/10.3390/ijms21207488 Cite
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Retinoic Acid-Responsive CD8 Effector T-cells Are Selectively Increased in IL-23-Rich Tissue in Gastrointestinal GvHD

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.
[Blood]
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Pellino1 Promotes Chronic Inflammatory Skin Disease via Keratinocyte Hyperproliferation and Induction of the T Helper 17 Response

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]
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Myeloid-Derived Suppressor Cell Depletion Therapy Targets IL-17A-Expressing Mammary Carcinomas

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.
[Scientific Reports]
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
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Microbiota-Dependent Expansion of Testicular IL-17-Producing Vγ6+ γδ T Cells upon Puberty Promotes Local Tissue Immune Surveillance

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.
[Mucosal Immunology]
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
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