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Nature Immunology

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https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#1
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28628091/the-btg2-prmt1-module-limits-pre-b-cell-expansion-by-regulating-the-cdk4-cyclin-d3-complex
#2
Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J Fiala, Susana Minguet, Bettina Warscheid, David M Tarlinton, Hassan Jumaa, David Medgyesi, Michael Reth
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28604720/igg-fc-domains-that-bind-c1q-but-not-effector-fc%C3%AE-receptors-delineate-the-importance-of-complement-mediated-effector-functions
#3
Chang-Han Lee, Gabrielle Romain, Wupeng Yan, Makiko Watanabe, Wissam Charab, Biliana Todorova, Jiwon Lee, Kendra Triplett, Moses Donkor, Oana I Lungu, Anja Lux, Nicholas Marshall, Margaret A Lindorfer, Odile Richard-Le Goff, Bianca Balbino, Tae Hyun Kang, Hidetaka Tanno, George Delidakis, Corrine Alford, Ronald P Taylor, Falk Nimmerjahn, Navin Varadarajan, Pierre Bruhns, Yan Jessie Zhang, George Georgiou
Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement...
June 12, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28604719/essential-role-for-gabarap-autophagy-proteins-in-interferon-inducible-gtpase-mediated-host-defense
#4
Miwa Sasai, Naoya Sakaguchi, Ji Su Ma, Shuhei Nakamura, Tsuyoshi Kawabata, Hironori Bando, Youngae Lee, Tatsuya Saitoh, Shizuo Akira, Akiko Iwasaki, Daron M Standley, Tamotsu Yoshimori, Masahiro Yamamoto
Mammalian autophagy-related 8 (Atg8) homologs consist of LC3 proteins and GABARAPs, all of which are known to be involved in canonical autophagy. In contrast, the roles of Atg8 homologs in noncanonical autophagic processes are not fully understood. Here we show a unique role of GABARAPs, in particular gamma-aminobutyric acid (GABA)-A-receptor-associated protein-like 2 (Gabarapl2; also known as Gate-16), in interferon-γ (IFN-γ)-mediated antimicrobial responses. Cells that lacked GABARAPs but not LC3 proteins and mice that lacked Gate-16 alone were defective in the IFN-γ-induced clearance of vacuolar pathogens such as Toxoplasma...
June 12, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28604718/the-transcription-factor-runx3-guards-cytotoxic-cd8-effector-t-cells-against-deviation-towards-follicular-helper-t-cell-lineage
#5
Qiang Shan, Zhouhao Zeng, Shaojun Xing, Fengyin Li, Stacey M Hartwig, Jodi A Gullicksrud, Samarchith P Kurup, Natalija Van Braeckel-Budimir, Yao Su, Matthew D Martin, Steven M Varga, Ichiro Taniuchi, John T Harty, Weiqun Peng, Vladimir P Badovinac, Hai-Hui Xue
Activated CD8(+) T cells differentiate into cytotoxic effector (TEFF) cells that eliminate target cells. How TEFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in TEFF cells. Runx3-deficient CD8(+) TEFF cells aberrantly upregulated genes characteristic of follicular helper T (TFH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the TFH program...
June 12, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28553952/the-a946t-variant-of-the-rna-sensor-ifih1-mediates-an-interferon-program-that-limits-viral-infection-but-increases-the-risk-for-autoimmunity
#6
Jacquelyn A Gorman, Christian Hundhausen, John S Errett, Amy E Stone, Eric J Allenspach, Yan Ge, Tanvi Arkatkar, Courtnee Clough, Xuezhi Dai, Socheath Khim, Kathleen Pestal, Denny Liggitt, Karen Cerosaletti, Daniel B Stetson, Richard G James, Mohamed Oukka, Patrick Concannon, Michael Gale, Jane H Buckner, David J Rawlings
The single-nucleotide polymorphism rs1990760 in the gene encoding the cytosolic viral sensor IFIH1 results in an amino-acid change (A946T; IFIH1(T946)) that is associated with multiple autoimmune diseases. The effect of this polymorphism on both viral sensing and autoimmune pathogenesis remains poorly understood. Here we found that human peripheral blood mononuclear cells (PBMCs) and cell lines expressing the risk variant IFIH1(T946) exhibited heightened basal and ligand-triggered production of type I interferons...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28553951/post-translational-control-of-t-cell-development-by-the-escrt-protein-chmp5
#7
Stanley Adoro, Kwang Hwan Park, Sarah E Bettigole, Raphael Lis, Hee Rae Shin, Heewon Seo, Ju Han Kim, Klaus-Peter Knobeloch, Jae-Hyuck Shim, Laurie H Glimcher
The acquisition of a protective vertebrate immune system hinges on the efficient generation of a diverse but self-tolerant repertoire of T cells by the thymus through mechanisms that remain incompletely resolved. Here we identified the endosomal-sorting-complex-required-for-transport (ESCRT) protein CHMP5, known to be required for the formation of multivesicular bodies, as a key sensor of thresholds for signaling via the T cell antigen receptor (TCR) that was essential for T cell development. CHMP5 enabled positive selection by promoting post-selection thymocyte survival in part through stabilization of the pro-survival protein Bcl-2...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28553950/atypical-chemokine-receptor-1-on-nucleated-erythroid-cells-regulates-hematopoiesis
#8
Johan Duchene, Igor Novitzky-Basso, Aude Thiriot, Maria Casanova-Acebes, Mariaelvy Bianchini, S Leah Etheridge, Elin Hub, Katrin Nitz, Katharina Artinger, Kathrin Eller, Jorge Caamaño, Thomas Rülicke, Paul Moss, Remco T A Megens, Ulrich H von Andrian, Andres Hidalgo, Christian Weber, Antal Rot
Healthy individuals of African ancestry have neutropenia that has been linked with the variant rs2814778(G) of the gene encoding atypical chemokine receptor 1 (ACKR1). This polymorphism selectively abolishes the expression of ACKR1 in erythroid cells, causing a Duffy-negative phenotype. Here we describe an unexpected fundamental role for ACKR1 in hematopoiesis and provide the mechanism that links its absence with neutropenia. Nucleated erythroid cells had high expression of ACKR1, which facilitated their direct contact with hematopoietic stem cells...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#9
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530713/bach2-immunodeficiency-illustrates-an-association-between-super-enhancers-and-haploinsufficiency
#10
Behdad Afzali, Juha Grönholm, Jana Vandrovcova, Charlotte O'Brien, Hong-Wei Sun, Ine Vanderleyden, Fred P Davis, Ahmad Khoder, Yu Zhang, Ahmed N Hegazy, Alejandro V Villarino, Ira W Palmer, Joshua Kaufman, Norman R Watts, Majid Kazemian, Olena Kamenyeva, Julia Keith, Anwar Sayed, Dalia Kasperaviciute, Michael Mueller, Jason D Hughes, Ivan J Fuss, Mohammed F Sadiyah, Kim Montgomery-Recht, Joshua McElwee, Nicholas P Restifo, Warren Strober, Michelle A Linterman, Paul T Wingfield, Holm H Uhlig, Rahul Roychoudhuri, Timothy J Aitman, Peter Kelleher, Michael J Lenardo, John J O'Shea, Nichola Cooper, Arian D J Laurence
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#11
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28504698/dendritic-cells-enter-lymph-vessels-by-hyaluronan-mediated-docking-to-the-endothelial-receptor-lyve-1
#12
Louise A Johnson, Suneale Banerji, William Lawrance, Uzi Gileadi, Gennaro Prota, Kayla A Holder, Yaowaluck M Roshorm, Tomáš Hanke, Vincenzo Cerundolo, Nicholas W Gale, David G Jackson
Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8(+) T cell responses in skin-draining LNs...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28504697/the-transcriptional-coactivator-taz-regulates-reciprocal-differentiation-of-th17-cells-and-treg-cells
#13
Jing Geng, Shujuan Yu, Hao Zhao, Xiufeng Sun, Xun Li, Ping Wang, Xiaolin Xiong, Lixin Hong, Changchuan Xie, Jiahui Gao, Yiran Shi, Jiaqi Peng, Randy L Johnson, Nengming Xiao, Linrong Lu, Jiahuai Han, Dawang Zhou, Lanfen Chen
An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under TH17 cell-inducing conditions and was required for TH17 differentiation and TH17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28481329/yap-antagonizes-innate-antiviral-immunity-and-is-targeted-for-lysosomal-degradation-through-ikk%C3%A9-mediated-phosphorylation
#14
Shuai Wang, Feng Xie, Feng Chu, Zhengkui Zhang, Bing Yang, Tong Dai, Liang Gao, Lin Wang, Li Ling, Junling Jia, Hans van Dam, Jin Jin, Long Zhang, Fangfang Zhou
The transcription regulator YAP controls organ size by regulating cell growth, proliferation and apoptosis. However, whether YAP has a role in innate antiviral immunity is largely unknown. Here we found that YAP negatively regulated an antiviral immune response. YAP deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in vivo. YAP blocked dimerization of the transcription factor IRF3 and impeded translocation of IRF3 to the nucleus after viral infection. Notably, virus-activated kinase IKKɛ phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28632722/learning-during-inflammation
#15
Zoltan Fehervari
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28632721/il-22-in-peyer-s-patches
#16
Laurie A Dempsey
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28632720/highly-localized-memory
#17
Zoltan Fehervari
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28632719/a-rheostat-tuning-thymic-selection
#18
Gerald P Morris, Stephen M Hedrick
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28632718/epigenetic-changes-in-tils
#19
Laurie A Dempsey
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28632717/polymorphisms-in-ifih1-the-good-and-the-bad
#20
Erika Della Mina, Mathieu P Rodero, Yanick J Crow
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
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