An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells

Researchers present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules.
[Cell]
da Silva, C. O., Gicquel, T., Daniel, Y., Bártholo, T., Vène, E., Loyer, P., Pôrto, L. C., Lagente, V., & Victoni, T. (2020). Alteration of immunophenotype of human macrophages and monocytes after exposure to cigarette smoke. Scientific Reports, 10(1), 12796. https://doi.org/10.1038/s41598-020-68753-1 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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LRCH1 Deficiency Enhances LAT Signalosome Formation and CD8+ T Cell Responses against Tumors and Pathogens

Investigators demonstrated that LRCH1 directly bound linker for activation of T cells (LAT), reduced LAT phosphorylation and interaction with GRB2, and also promoted the endocytosis of LAT.
[Proceedings of the National Academy of Sciences of the United States of America]
Liu, C., Xu, X., Han, L., Wan, X., Zheng, L., Li, C., Liao, Z., Xiao, J., Zhong, R., Zheng, X., Wang, Q., Li, Z., Chen, H., Wei, B., & Wang, H. (2020). LRCH1 deficiency enhances LAT signalosome formation and CD8+ T cell responses against tumors and pathogens. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2000970117 Cite
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Multiple Signaling Roles of CD3ε and Its Application in CAR-T Cell Therapy

Scientists found that incorporation of the CD3ε cytoplasmic domain into a second-generation chimeric antigen receptor (CAR) improved antitumor activity of CAR-T cells.
[Cell]
Wu, W., Zhou, Q., Masubuchi, T., Shi, X., Li, H., Xu, X., Huang, M., Meng, L., He, X., Zhu, H., Gao, S., Zhang, N., Jing, R., Sun, J., Wang, H., Hui, E., Wong, C. C., & Xu, C. (2020). Multiple Signaling Roles of CD3ε and Its Application in CAR-T Cell Therapy. Cell, 0(0). https://doi.org/10.1016/j.cell.2020.07.018 Cite
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The Cytokine Receptor IL-7Rα Impairs IL-2 Receptor Signaling and Constrains the In Vitro Differentiation of Foxp3+ Treg Cells

Researchers report that IL-7Rα downregulation was necessary to maximize IL-2R signaling. While IL-7Rα overexpression promoted IL-7 signaling, unexpectedly, IL-2 signaling was suppressed in the same cells.
[iScience]
Waickman, A. T., Keller, H. R., Kim, T.-H., Luckey, M. A., Tai, X., Hong, C., Molina-Paris, C., Walsh, S. T. R., & Park, J.-H. (2020). The cytokine receptor IL-7Rα impairs IL-2 receptor signaling and constrains the in vitro differentiation of Foxp3+ Treg cells. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101421 Cite
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PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells

Scientists found that PTPN2 deficiency renders cells in vivo and in vitro less dependent on survival-promoting cytokines, such as interleukin (IL)-2 and IL-15.
[Cell Reports]
Flosbach, M., Oberle, S. G., Scherer, S., Zecha, J., Hoesslin, M. von, Wiede, F., Chennupati, V., Cullen, J. G., List, M., Pauling, J. K., Baumbach, J., Kuster, B., Tiganis, T., & Zehn, D. (2020). PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells. Cell Reports, 32(4). https://doi.org/10.1016/j.celrep.2020.107957 Cite
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Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium

Although both caspase-1 and caspase-11 could cleave gasdermin D in macrophages and neutrophils, researchers found that NLRC4-activated caspase-1 triggered pyroptosis in macrophages, but this pathway did not trigger pyroptosis in neutrophils.
[Cell Reports]
Kovacs, S. B., Oh, C., Maltez, V. I., McGlaughon, B. D., Verma, A., Miao, E. A., & Aachoui, Y. (2020). Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium. Cell Reports, 32(4). https://doi.org/10.1016/j.celrep.2020.107967 Cite
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Neonatal Genetics of Gene Expression Reveal Potential Origins of Autoimmune and Allergic Disease Risk

Investigators mapped expression quantitative trait loci in resting myeloid cells and CD4+ T cells from cord blood samples, as well as in response to lipopolysaccharide or phytohemagglutinin stimulation, respectively.
[Nature Communications]
Huang, Q. Q., Tang, H. H. F., Teo, S. M., Mok, D., Ritchie, S. C., Nath, A. P., Brozynska, M., Salim, A., Bakshi, A., Holt, B. J., Khor, C. C., Sly, P. D., Holt, P. G., Holt, K. E., & Inouye, M. (2020). Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk. Nature Communications, 11(1), 3761. https://doi.org/10.1038/s41467-020-17477-x Cite
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Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Mass cytometry was performed on peripheral blood mononuclear cells from primary biliary cholangitis patients and age-/sex-matched healthy controls to obtain immune cell abundance and marker expression profiles.
[Scientific Reports]
Jang, J. S., Juran, B. D., Cunningham, K. Y., Gupta, V. K., Son, Y. M., Yang, J. D., Ali, A. H., Enninga, E. A. L., Sung, J., & Lazaridis, K. N. (2020). Single-cell mass cytometry on peripheral blood identifies immune cell subsets associated with primary biliary cholangitis. Scientific Reports, 10(1), 12584. https://doi.org/10.1038/s41598-020-69358-4 Cite
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CD4 T Cell-Intrinsic Role for the T Helper 17 Signature Cytokine IL-17: Effector Resistance to Immune Suppression

The authors demonstrated that human CD4+ T cells exposed to a Th17-differentiating milieu were significantly more resistant to immune suppression by CD8+ T cells compared to control Th0 cells.
[Proceedings of the National Academy of Sciences of the United States of America]
Crawford, M. P., Sinha, S., Renavikar, P. S., Borcherding, N., & Karandikar, N. J. (2020). CD4 T cell-intrinsic role for the T helper 17 signature cytokine IL-17: Effector resistance to immune suppression. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2005010117 Cite
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Pathogenic Autoimmunity in Atherosclerosis Evolves from Initially Protective ApoB-Reactive CD4+ T-Regulatory Cells

To interrogate the function of autoreactive CD4+ T cells in atherosclerosis, researchers used a novel tetramer of MHC-II to track T cells reactive to the mouse self-peptide ApoB978-993 on a single cell level.
[Circulation]
Wolf Dennis, Gerhardt Teresa, Winkels Holger, Anto Michel Nathaly, Pramod Akula Bala, Ghosheh Yanal, Brunel Simon, Buscher Konrad, Miller Jacqueline, McArdle Sara, Baas Livia, Kobiyama Kouji, Vassallo Melanie, Ehinger Erik, Dileepan Thamotharampillai, Ali Amal, Schell Maximilian, Mikulski Zbigniew, Sidler Daniel, … Ley Klaus. (n.d.). Pathogenic Autoimmunity in Atherosclerosis Evolves from Initially Protective ApoB-Reactive CD4+ T-Regulatory Cells. Circulation, 0(0). https://doi.org/10.1161/CIRCULATIONAHA.119.042863 Cite
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Transcriptome Profiling Identifies TIGIT as a Marker of T Cell Exhaustion in Liver Cancer

Investigators performed for the first time a comprehensive mRNA profiling of CD8 T cells in a murine model of autochthonous liver cancer by comparing the transcriptome of naive, functional effector and exhausted, tumor‐specific CD8 T cells.
[Hepatology]
Ostroumov, D., Duong, S., Wingerath, J., Woller, N., Manns, M. P., Timrott, K., Kleine, M., Ramackers, W., Roessler, S., Nahnsen, S., Czemmel, S., Dittrich‐Breiholz, O., Eggert, T., Kühnel, F., & Wirth, T. C. (n.d.). Transcriptome profiling identifies TIGIT as a marker of T cell exhaustion in liver cancer. Hepatology, n/a(n/a). https://doi.org/10.1002/hep.31466 Cite
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