Nature Immunology Contents: November 2012 Volume 13 pp 1021 - 1128

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Produced with support from Novartis Pharma AG   Editorial Top Resources for life   p1021 doi:10.1038/ni.2458 Meeting Report Top Therapeutic potential of targeting IL-17   pp1022 - 1025 Sarah A Jones, Caroline E Sutton, Daniel Cua and Kingston H G Mills doi:10.1038/ni.2450 News and Views Top TBK1 suppression of IgA in the NIK of time   pp1027 - 1029 Richard J Bram doi:10.1038/ni.2451 The kinase TBK1 participates in signaling pathways that induce antimicrobial responses. TBK1 is also necessary for the suppression of excessive production of immunoglobulin A by accelerating destruction of the kinase NIK. See also: Article by Jin et al. The case of the missing c-Myc   pp1029 - 1031 Arthur L Shaffer III and Louis M Staudt doi:10.1038/ni.2455 A fundamental mystery of the biology of germinal center B cells is why it seems that these rapidly dividing B cells lack expression of c-Myc, a transcriptional regulator intimately linked to cell metabolism and proliferation. This mystery has now been resolved. See also: Article by Dominguez-Sola et al. | Article by Calado et al. Balancing pro- and anti-inflammatory TLR4 signaling   pp1031 - 1033 Sabine Siegemund and Karsten Sauer doi:10.1038/ni.2452 Limiting immune responses is critical for protecting the host from harm. The p110δ isoform of the kinase PI(3)K acts as a balance between pro- and anti-inflammatory TLR4 signaling in dendritic cells. See also: Article by Aksoy et al. The ubiquitous nature of IL-17   pp1034 - 1035 Averil I Ma doi:10.1038/ni.2448 The deubiquitinating enzyme USP25 restricts ubiquitination of the adaptors TRAF5 and TRAF6 and signaling via interleukin 17 and thus joins several ubiquitin-modifying enzymes already known to regulate this biomedically important pathway. See also: Article by Zhong et al. Immunology JOBS of the week Postdoctoral Position in Immunology University of Zurich - Faculty of Medicine Bioinformatics Postdoc for Immunology Applications La Jolla Institute for Allergy & Immunology Research Technician in Immunology Imperial College London Postdoctoral Fellow, Immunology / Neuroimmunology Research Thomas Jefferson University Open Rank Faculty Position and Postdocs in Immunology Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences More Science jobs from Immunology EVENT Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances 2nd Dec - 5th Dec 2012 FL, US More science events from Research Highlights Top Strategic locations | Composite AICE recognition | NET benefits | Intrinsic neuronal immunity | Autoimmunity thresholds | Allies for weight loss Review Top Cytokines of the γc family control CD4+ T cell differentiation and function   pp1037 - 1044 Hidehiro Yamane and William E Paul doi:10.1038/ni.2431 Advertisement Visit the New mpbio.com It''s Never Been Easier to... Find your favorite products Explore new products and applications Place orders online View your order history and status Search and find technical documents ...on the NEW mpbio.com   Articles Top The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock   pp1045 - 1054 Ezra Aksoy, Salma Taboubi, David Torres, Sandrine Delbauve, Abderrahman Hachani, Maria A Whitehead, Wayne P Pearce, Inma Berenjeno-Martin, Gemma Nock, Alain Filloux, Rudi Beyaert, Veronique Flamand and Bart Vanhaesebroeck doi:10.1038/ni.2426 TLR4 signaling shifts from plasma membrane TIRAP-MyD88-mediated pathways to endosomal TRAM-TRIF-mediated signaling. Vanhaesebroeck and colleagues show that the kinase PI(3)K p110δ is required for TLR4 internalization and degradation of TIRAP. See also: News and Views by Siegemund & Sauer Pellino3 targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons   pp1055 - 1062 Jakub Siednienko, Ruaidhri Jackson, Mark Mellett, Nezira Delagic, Shuo Yang, Bingwei Wang, Lisa S Tang, John J Callanan, Bernard P Mahon and Paul N Moynagh doi:10.1038/ni.2429 Signaling through toll-like receptors induces cytokines and type I interferon. Moynagh and colleagues show that the E3 ubiquitin ligase Pellino3 specifically represses the expression of type I interferon in response to TLR3 activation. Inhibition of TLR signaling by a bacterial protein containing immunoreceptor tyrosine-based inhibitory motifs   pp1063 - 1071 Dapeng Yan, Xingyu Wang, Lijun Luo, Xuetao Cao and Baoxue Ge doi:10.1038/ni.2417 Successful pathogens can overcome innate immune defenses. Ge and colleagues show that Tir protein expressed by enteropathogenic Escherichia coli is injected into host cells, where it interferes with adaptor TRAF6-dependent signaling. Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow   pp1072 - 1082 Aya Ludin, Tomer Itkin, Shiri Gur-Cohen, Alexander Mildner, Elias Shezen, Karin Golan, Orit Kollet, Alexander Kalinkovich, Ziv Porat, Gabriele D'Uva, Amir Schajnovitz, Elena Voronov, David A Brenner, Ron N Apte, Steffen Jung and Tsvee Lapidot doi:10.1038/ni.2408 Hematopoietic stem cells must be shielded from toxic and inflammatory insults to ensure lifelong blood cell production. Lapidot and colleagues identify a rare bone marrow macrophage population that protects hematopoietic stem cells. The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry   pp1083 - 1091 David Dominguez-Sola, Gabriel D Victora, Carol Y Ying, Ryan T Phan, Masumichi Saito, Michel C Nussenzweig and Riccardo Dalla-Favera doi:10.1038/ni.2428 The molecular control of germinal center selection is still being determined. Dalla-Favera and colleagues show that the cell-cycle regulator c-Myc is essential for B cell selection and reentry into the germinal center. See also: News and Views by Shaffer & Staudt The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers   pp1092 - 1100 Dinis Pedro Calado, Yoshiteru Sasaki, Susana A Godinho, Alex Pellerin, Karl Köchert, Barry P Sleckman, Ignacio Moreno de Alborán, Martin Janz, Scott Rodig and Klaus Rajewsky doi:10.1038/ni.2418 The regulator c-Myc is well known for controlling cell growth but, paradoxically, evidence for its involvement in germinal centers has proven elusive. Rajewsky and colleagues show that it is essential for their development and maintenance. See also: News and Views by Shaffer & Staudt The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling   pp1101 - 1109 Jin Jin, Yichuan Xiao, Jae-Hoon Chang, Jiayi Yu, Hongbo Hu, Robyn Starr, George C Brittain, Mikyoung Chang, Xuhong Cheng and Shao-Cong Sun doi:10.1038/ni.2423 How isotype-specific immunoglobulin production is regulated is largely unknown. Sun and colleagues show that the kinase TBK1 acts as a negative regulator of IgA class switching by attenuating NIK-mediated NF-κB signaling. See also: News and Views by Bram Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25   pp1110 - 1117 Bo Zhong, Xikui Liu, Xiaohu Wang, Seon Hee Chang, Xindong Liu, Aibo Wang, Joseph M Reynolds and Chen Dong doi:10.1038/ni.2427 How IL-17 signaling is regulated remains poorly understood. Dong and colleagues identify the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation. See also: News and Views by Ma Resource Top Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages   pp1118 - 1128 Emmanuel L Gautier, Tal Shay, Jennifer Miller, Melanie Greter, Claudia Jakubzick, Stoyan Ivanov, Julie Helft, Andrew Chow, Kutlu G Elpek, Simon Gordonov, Amin R Mazloom, Avi Ma'ayan, Wei-Jen Chua, Ted H Hansen, Shannon J Turley, Miriam Merad, Gwendalyn J Randolph and the Immunological Genome Consortium:  Emmanuel L Gautier, Claudia Jakubzick, Gwendalyn J Randolph, Adam J Best, Jamie Knell, Ananda Goldrath, Jennifer Miller, Brian Brown, Miriam Merad, Vladimir Jojic, Daphne Koller, Nadia Cohen, Patrick Brennan, Michael Brenner, Tal Shay, Aviv Regev, Anne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley, Radu Jianu, David Laidlaw, Jim Collins, Kavitha Narayan, Katelyn Sylvia, Joonsoo Kang, Roi Gazit, Brian S Garrison, Derrick J Rossi, Francis Kim, Tata Nageswara Rao, Amy Wagers, Susan A Shinton, Richard R Hardy, Paul Monach, Natalie A Bezman, Joseph C Sun, Charlie C Kim, Lewis L Lanier, Tracy Heng, Taras Kreslavsky, Michio Painter, Jeffrey Ericson, Scott Davis, Diane Mathis and Christophe Benoist doi:10.1038/ni.2419 By comparing gene-expression profiles, Randolph and colleagues distinguish different types of macrophages and pinpoint the differences between macrophages and dendritic cells. 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