Table of contents


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Editorial

Hyping research p795

doi:10.1038/ni0809-795

Reporting of scientific research is sometimes exaggerated or at worse inaccurate. Researchers need to change this and have the power to do so.


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Obituary

Jean Dausset 1916–2009 p797

Edgardo D Carosella

doi:10.1038/ni0809-797


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Commentary

RNAi screening: tips and techniques pp799 - 804

Sonia Sharma & Anjana Rao

doi:10.1038/ni0809-799

By identifying gene products whose knockdown is associated with phenotypic changes, large-scale RNA-mediated interference screens have demonstrated previously unknown components of biological pathways. This commentary provides general guidelines for using such screens to answer questions of immunological interest.


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News and Views

Themis imposes new law and order on positive selection pp805 - 806

Paul M Allen

doi:10.1038/ni0809-805

The molecular mechanism by which thymocytes are positively selected remains incompletely understood. Three studies add a new piece to the positive selection puzzle.

See also: Article by Johnson et al. | Article by Lesourne et al. | Article by Fu et al.


TH2 bias: Mina tips the balance pp806 - 808

Saskia Hemmers & Kerri A Mowen

doi:10.1038/ni0809-806

Tipping the balance of early cytokine production can lead to lineage bias and, potentially, immune-mediated pathology. Mapping of a leishmania-susceptibility region has identified a gene that may determine the extent of T helper type 2 bias in naive helper T cells.

See also: Article by Okamoto et al.


New insight into the everlasting host-pathogen arms race pp808 - 809

Coenraad Kuijl & Jacques Neefjes

doi:10.1038/ni0809-808

New work explains how the interferon-gamma-regulated GTPase Irgm1 on phagosomes responds to intracellular signaling and recruits the 'machinery' for fusion with lysosomes. This pathway overlaps a signaling route controlled by bacteria to prevent the fusion of phagosomes with lysosomes.

See also: Article by Tiwari et al.


Dead man walking: how thymocytes scan the medulla pp809 - 811

Ludger Klein

doi:10.1038/ni0809-809

The thymic medulla provides a unique milieu for the induction of T cell tolerance. New work now provides a first glimpse of how thymocytes scan this microenvironment and thus maximize their chances of encountering self antigen.

See also: Article by Le Borgne et al.


One problem, two solutions pp811 - 813

Thomas Boehm

doi:10.1038/ni0809-811

Jawless fishes, the 'sister' group of jawed vertebrates, use leucine-rich repeat–containing proteins as antigen receptors. New work shows that the two isotypes of variable lymphocyte receptors are expressed in distinct lymphocyte lineages, which indicates that lymphocytes resembling T cells and B cells are an ancient feature of all vertebrates.


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Research Highlights

Research Highlights p815

doi:10.1038/ni0809-815


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Perspective

RAG: a recombinase diversified pp817 - 821

Adam G W Matthews & Marjorie A Oettinger

doi:10.1038/ni.1776


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Articles

The impact of negative selection on thymocyte migration in the medulla pp823 - 830

Marie Le Borgne, Ena Ladi, Ivan Dzhagalov, Paul Herzmark, Ying Fang Liao, Arup K Chakraborty & Ellen A Robey

doi:10.1038/ni.1761

Self-reactive thymocytes are eliminated through negative selection in the thymic medulla. Robey and colleagues find that autoreactive thymocytes show slower and more confined migration than that of polyclonal thymocytes in the medulla.

See also: News and Views by Klein


Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection pp831 - 839

Andy L Johnson, L Aravind, Natalia Shulzhenko, Andre Morgun, See-Young Choi, Tanya L Crockford, Teresa Lambe, Heather Domaschenz, Edyta M Kucharska, Lixin Zheng, Carola G Vinuesa, Michael J Lenardo, Christopher C Goodnow, Richard J Cornall & Ronald H Schwartz

doi:10.1038/ni.1769

The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.

See also: News and Views by Allen | Article by Lesourne et al. | Article by Fu et al.


Themis, a T cell–specific protein important for late thymocyte development pp840 - 847

Renaud Lesourne, Shoji Uehara, Jan Lee, Ki-Duk Song, LiQi Li, Julia Pinkhasov, Yongqing Zhang, Nan-Ping Weng, Kathryn F Wildt, Lie Wang, Remy Bosselut & Paul E Love

doi:10.1038/ni.1768

The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.

See also: News and Views by Allen | Article by Johnson et al. | Article by Fu et al.


Themis controls thymocyte selection through regulation of T cell antigen receptor–mediated signaling pp848 - 856

Guo Fu, Sébastien Vallée, Vasily Rybakin, Marielena V McGuire, Jeanette Ampudia, Claudia Brockmeyer, Mogjiborahman Salek, Paul R Fallen, John A H Hoerter, Anil Munshi, Yina H Huang, Jianfang Hu, Howard S Fox, Karsten Sauer, Oreste Acuto & Nicholas R J Gascoigne

doi:10.1038/ni.1766

The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.

See also: News and Views by Allen | Article by Johnson et al. | Article by Lesourne et al.


Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells pp857 - 863

Thomas Duhen, Rebekka Geiger, David Jarrossay, Antonio Lanzavecchia & Federica Sallusto

doi:10.1038/ni.1767

Helper T cells become polarized to effect a 'division of labor'. Sallusto and Spits and colleagues identify a new subset of skin-homing helper T cells, TH-22 cells, that secrete interleukin 22.


Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells pp864 - 871

Sara Trifari, Charles D Kaplan, Elise H Tran, Natasha K Crellin & Hergen Spits

doi:10.1038/ni.1770

Helper T cells become polarized to effect a 'division of labor'. Sallusto and Spits and colleagues identify a new subset of skin-homing helper T cells, TH-22 cells, that secrete interleukin 22.


Mina, an Il4 repressor, controls T helper type 2 bias pp872 - 879

Mariko Okamoto, Melanie Van Stry, Linda Chung, Madoka Koyanagi, Xizhang Sun, Yoshie Suzuki, Osamu Ohara, Hiroshi Kitamura, Atsushi Hijikata, Masato Kubo & Mark Bix

doi:10.1038/ni.1747

Mouse strains show varying inherent biases to T helper type 2 (TH2) responses. Bix and colleagues identify Mina, a jumonji C protein, as a negative regulator of the gene encoding interleukin 4 whose expression inversely correlates with TH2 bias.

See also: News and Views by Hemmers & Mowen


Essential function for the GTPase TC21 in homeostatic antigen receptor signaling pp880 - 888

Pilar Delgado, Beatriz Cubelos, Enrique Calleja, Nuria Martínez-Martín, Angel Ciprés, Isabel Mérida, Carmen Bellas, Xosé R Bustelo & Balbino Alarcón

doi:10.1038/ni.1749

Tonic antigen receptor signaling contributes to the homeostasis of naive lymphocytes. Alarcón and colleagues show that resting lymphocytes transmit tonic antigen receptor signals through the GTPase TC21 to trigger the PI(3)K pathway.


Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell–stimulating programs in basophils pp889 - 898

Kang Chen, Weifeng Xu, Melanie Wilson, Bing He, Norman W Miller, Eva Bengtén, Eva-Stina Edholm, Paul A Santini, Poonam Rath, April Chiu, Marco Cattalini, Jiri Litzman, James B Bussel, Bihui Huang, Antonella Meini, Kristian Riesbeck, Charlotte Cunningham-Rundles, Alessandro Plebani & Andrea Cerutti

doi:10.1038/ni.1748

Mature B cells express immunoglobulin D, but its function is unknown. Cerutti and colleagues show that respiratory mucosal B cells secrete immunoglobulin D, which activates basophils and enhances antimicrobial function.


Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair pp899 - 906

Maziar Divangahi, Minjian Chen, Huixian Gan, Danielle Desjardins, Tyler T Hickman, David M Lee, Sarah Fortune, Samuel M Behar & Heinz G Remold

doi:10.1038/ni.1758

Macrophages infected with virulent Mycobacterium tuberculosis die by necrosis. Remold and colleagues show that virulent M. tuberculosis promotes necrosis by damaging the plasma membrane and inhibiting its repair.


Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P2 and PtdIns(3,4,5)P3 promotes immunity to mycobacteria pp907 - 917

Sangeeta Tiwari, Han-Pil Choi, Takeshi Matsuzawa, Marc Pypaert & John D MacMicking

doi:10.1038/ni.1759

Immunity-related GTPase 1 (Irgm1) is needed for defense against bacteria that reside in phagosomes of macrophages. MacMicking and colleagues identify molecular mediators that act 'upstream' and 'downstream' of Irgm1 in the phagosomal membrane.

See also: News and Views by Kuijl & Neefjes


A TNF- and c-Cbl-dependent FLIPS-degradation pathway and its function in Mycobacterium tuberculosis–induced macrophage apoptosis pp918 - 926

Manikuntala Kundu, Sushil Kumar Pathak, Kuldeep Kumawat, Sanchita Basu, Gargi Chatterjee, Shresh Pathak, Takuya Noguchi, Kohsuke Takeda, Hidenori Ichijo, Christine B F Thien, Wallace Y Langdon & Joyoti Basu

doi:10.1038/ni.1754

Apoptosis of Mycobacterium tuberculosis (Mtb)-infected macrophages restricts the spread of infection. Basu and colleagues delineate the signaling pathway needed for death of Mtb-infected cells.


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