Time and money well spent - p1085

doi:10.1038/ni1008-1085

The sometimes arduous effort that went toward securing and distributing state government funds for broader stem cell work should be lauded, not lamented.

Full Text - Time and money well spent | PDF (188 KB) - Time and money well spent

Immunology south of the equator in the Americas - pp1087 - 1090

Gabriel A Rabinovich, Alexis M Kalergis, Norberto W Zwirner & Wilson Savino

doi:10.1038/ni1008-1087

Abstract - | Full Text - Immunology south of the equator in the Americas | PDF (332 KB) - Immunology south of the equator in the Americas

The Immunological Genome Project: networks of gene expression in immune cells - pp1091 - 1094

Tracy S P Heng, Michio W Painter, The Immunological Genome Project Consortium, Kutlu Elpek, Veronika Lukacs-Kornek, Nora Mauermann, Shannon J Turley, Daphne Koller, Francis S Kim, Amy J Wagers, Natasha Asinovski, Scott Davis, Marlys Fassett, Markus Feuerer, Daniel H D Gray, Sokol Haxhinasto, Jonathan A Hill, Gordon Hyatt, Catherine Laplace, Kristen Leatherbee, Diane Mathis, Christophe Benoist, Radu Jianu, David H Laidlaw, J Adam Best, Jamie Knell, Ananda W Goldrath, Jessica Jarjoura, Joseph C Sun, Yanan Zhu, Lewis L Lanier, Ayla Ergun, Zheng Li, James J Collins, Susan A Shinton, Richard R Hardy, Randall Friedline, Katelyn Sylvia & Joonsoo Kang

doi:10.1038/ni1008-1091

Abstract - | Full Text - The Immunological Genome Project: networks of gene expression in immune cells | PDF (304 KB) - The Immunological Genome Project: networks of gene expression in immune cells

Putting ThPOK in place - pp1095 - 1096

J Jeremiah Bell & Avinash Bhandoola

doi:10.1038/ni1008-1095

ThPOK is necessary for the differentiation of CD4⁺ helper T cells. Three new studies indicate that, unexpectedly, ThPOK is required only after initial specification to the CD4⁺ lineage.

Full Text - Putting ThPOK in place | PDF (269 KB) - Putting ThPOK in place

See also: Article by Muroi et al. | Article by Wang et al. | Article by Egawa & Littman

RAPping production of type I interferon in pDCs through mTOR - pp1097 - 1099

Mauro Costa-Mattioli & Nahum Sonenberg

doi:10.1038/ni1008-1097

The production of type I interferon—the first line of defense against virus infection and critical for innate immunity—in plasmacytoid dendritic cells relies on the mammalian target of rapamycin.

Full Text - RAPping production of type I interferon in pDCs through mTOR | PDF (795 KB) - RAPping production of type I interferon in pDCs through mTOR

See also: Article by Cao et al.

Sensing necrosis with Mincle - pp1099 - 1100

Gordon D Brown

doi:10.1038/ni1008-1099

The mechanisms that lead to inflammation after necrotic cell death are poorly understood. New data show that the C-type lectin Mincle is involved in this process.

Full Text - Sensing necrosis with Mincle | PDF (1,683 KB) - Sensing necrosis with Mincle

See also: Article by Yamasaki et al.

Tuberculosis: unsealing the apoptotic envelope - pp1101 - 1102

Steven A Porcelli & William R Jacobs Jr

doi:10.1038/ni1008-1101

Mycobacterium tuberculosis grows in macrophages but escapes these cells by triggering their death. New findings delineate how this pathogen controls macrophage death to favor bacterial survival and avoid host immunity.

Full Text - Tuberculosis: unsealing the apoptotic envelope | PDF (1,210 KB) - Tuberculosis: unsealing the apoptotic envelope

See also: Article by Gan et al.

Research Highlights - p1103

doi:10.1038/ni1008-1103

Full Text - Research Highlights | PDF (115 KB) - Research Highlights

Shouts, whispers and the kiss of death: directional secretion in T cells - pp1105 - 1111

Morgan Huse, Emily J Quann & Mark M Davis

doi:10.1038/ni.f.215

Abstract - | Full Text - Shouts, whispers and the kiss of death: directional secretion in T cells | PDF (3,082 KB) - Shouts, whispers and the kiss of death: directional secretion in T cells

Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate - pp1113 - 1121

Sawako Muroi, Yoshinori Naoe, Chizuko Miyamoto, Kaori Akiyama, Tomokatsu Ikawa, Kyoko Masuda, Hiroshi Kawamoto & Ichiro Taniuchi

doi:10.1038/ni.1650

The transcription factor ThPOK is required for CD4⁺ T cell differentiation. Groups led by Taniuchi, Bosselut and Littman define distinct functions for ThPOK and other transcription factors in commitment versus specification of the CD4⁺ T cell lineage.

Abstract - | Full Text - Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate | PDF (1,148 KB) - Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate | Supplementary information

See also: News and Views by Costa-Mattioli & Sonenberg | Article by Wang et al. | Article by Egawa & Littman

Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4⁺ T cells - pp1122 - 1130

Lie Wang, Kathryn F Wildt, Jinfang Zhu, Xianyu Zhang, Lionel Feigenbaum, Lino Tessarollo, William E Paul, B J Fowlkes & Rémy Bosselut

doi:10.1038/ni.1647

The transcription factor ThPOK is required for CD4⁺ T cell differentiation. Groups led by Taniuchi, Bosselut and Littman define distinct functions for ThPOK and other transcription factors in commitment versus specification of the CD4⁺ T cell lineage.

Abstract - | Full Text - Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4+ T cells | PDF (1,073 KB) - Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4+ T cells | Supplementary information

See also: News and Views by Costa-Mattioli & Sonenberg

ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage - pp1131 - 1139

Takeshi Egawa & Dan R Littman

doi:10.1038/ni.1652

The transcription factor ThPOK is required for CD4⁺ T cell differentiation. Groups led by Taniuchi, Bosselut and Littman define distinct functions for ThPOK and other transcription factors in commitment versus specification of the CD4⁺ T cell lineage.

Abstract - | Full Text - ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage | PDF (853 KB) - ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage | Supplementary information

See also: News and Views by Costa-Mattioli & Sonenberg | Article by Muroi et al. | Article by Wang et al.

Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity - pp1140 - 1147

Yoichi Maekawa, Yoshiaki Minato, Chieko Ishifune, Takeshi Kurihara, Akiko Kitamura, Hidefumi Kojima, Hideo Yagita, Mamiko Sakata-Yanagimoto, Toshiki Saito, Ichiro Taniuchi, Shigeru Chiba, Saburo Sone & Koji Yasutomo

doi:10.1038/ni.1649

How T cell cytotoxic activity is induced remains incompletely defined. Yasutomo and colleagues now show that Notch2 signals, in direct cooperation with the transcription factor CREB1, promote granzyme B expression.

Abstract - | Full Text - Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity | PDF (717 KB) - Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity | Supplementary information

The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells - pp1148 - 1156

Gaëtan Barbet, Marie Demion, Ivan C Moura, Nicolas Serafini, Thibaut Léger, François Vrtovsnik, Renato C Monteiro, Romain Guinamard, Jean-Pierre Kinet & Pierre Launay

doi:10.1038/ni.1648

How calcium signaling affects dendritic cell (DC) maturation and/or migration is unclear. Launay and colleagues show that absence of the TRPM4 cation channel impairs DC migration but leaves DC maturation unaltered.

Abstract - | Full Text - The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells | PDF (852 KB) - The calcium-activated nonselective cation channel TRPM4 is essential for the migration but not the maturation of dendritic cells | Supplementary information

Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway - pp1157 - 1164

Weiping Cao, Santhakumar Manicassamy, Hua Tang, Sudhir Pai Kasturi, Ali Pirani, Niren Murthy & Bali Pulendran

doi:10.1038/ni.1645

The mammalian target of rapamycin pathway regulates many essential cellular responses. Pulendran and colleagues show that this pathway is required for Toll-like receptor–mediated production of type I interferon by plasmacytoid dendritic cells.

Abstract - | Full Text - Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway | PDF (625 KB) - Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway | Supplementary information

See also: News and Views by Costa-Mattioli & Sonenberg

Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll - pp1165 - 1170

Laure El Chamy, Vincent Leclerc, Isabelle Caldelari & Jean-Marc Reichhart

doi:10.1038/ni.1643

Microbial sensors activate the Toll pathway in flies. Reichhart and colleagues identify the serine protease Grass, which acts in parallel with Persephone to cleave Toll-activating Spatzle in response to Gram-positive bacteria and fungi.

Abstract - | Full Text - Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll | PDF (432 KB) - Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll | Supplementary information

Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin - pp1171 - 1178

Karla L Lightfield, Jenny Persson, Sky W Brubaker, Chelsea E Witte, Jakob von Moltke, Eric A Dunipace, Thomas Henry, Yao-Hui Sun, Dragana Cado, William F Dietrich, Denise M Monack, Renée M Tsolis & Russell E Vance

doi:10.1038/ni.1646

The molecular components of inflammasomes and what they sense are poorly defined. Vance and colleagues now show the carboxy-terminal 35 amino acids of flagellin activate the inflammasome in a Naip5-dependent way.

Abstract - | Full Text - Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin | PDF (553 KB) - Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin | Supplementary information

Mincle is an ITAM-coupled activating receptor that senses damaged cells - pp1179 - 1188

Sho Yamasaki, Eri Ishikawa, Machie Sakuma, Hiromitsu Hara, Koji Ogata & Takashi Saito

doi:10.1038/ni.1651

The C-type lectin family member Mincle is expressed mainly on macrophages. Saito and colleagues show that the nuclear protein SAP130, released by dead cells, is a ligand of Mincle that drives proinflammatory cytokine production by macrophages.

Abstract - | Full Text - Mincle is an ITAM-coupled activating receptor that senses damaged cells | PDF (765 KB) - Mincle is an ITAM-coupled activating receptor that senses damaged cells | Supplementary information

See also: News and Views by Brown

Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence - pp1189 - 1197

Huixian Gan, Jinhee Lee, Fucheng Ren, Minjian Chen, Hardy Kornfeld & Heinz G Remold

doi:10.1038/ni.1654

Virulent strains of Mycobacterium tuberculosis cause necrotic death of infected macrophages, which promotes bacterial dissemination. Remold and colleagues demonstrate that mycobacteria inhibit formation of the apoptotic envelope on macrophages, thus causing necrosis.

Abstract - | Full Text - Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence | PDF (580 KB) - Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence | Supplementary information

See also: News and Views by Porcelli & Jacobs Jr

Corrigendum: Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells - p1198

Boyd Butler, Diana H Kastendieck & John A Cooper

doi:10.1038/ni1008-1198

Full Text - Corrigendum: Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells | PDF (127 KB) - Corrigendum: Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cells