Insights 2326 The dream of Staphylococcal vaccination Patrick M. Schlievert 2326 A Mad(2) modification modulating megakaryopoiesis Adam Goldfarb 2327 Immunotherapy and the belly of the beast Taha Merghoub and Jedd D. Wolchok 2328 THE JOURNAL OF EXPERIMENTAL MEDICINE FLUshing in the bathroom VOLUME 211 NUMBER 12 NOVEMBER 17, 2014 www.jem.org Carolina Amezcua, Nicola Gagliani, and Richard Flavell 2329 Too much of a good thing: NLRC4 and autoinflammation Mark S. Anderson Brief Definitive Reports 2331 Staphylococcus aureus infection induces protein A–mediated immune evasion in humans Noel T. Pauli, Hwan Keun Kim, Fabiana Falugi, Min Huang, John Dulac, Carole Henry Dunand, Nai-Ying Zheng, Kaval Kaur, Sarah F. Andrews, Yunping Huang, Andrea DeDent, Karen M. Frank, Angella Charnot-Katsikas, Olaf Schneewind, and Patrick C. Wilson 2341 Sex steroid blockade enhances thymopoiesis by modulating Notch signaling Enrico Velardi, Jennifer J. Tsai, Amanda M. Holland, Tobias Wertheimer, Vionnie W.C. Yu, Johannes L. Zakrzewski, Andrea Z. Tuckett, Natalie V. Singer, Mallory L. West, Odette M. Smith, Lauren F. Young, Fabiana M. Kreines, Emily R. Levy, Richard L. Boyd, David T. Scadden, Jarrod A. Dudakov, and Marcel R.M. van den Brink 2351 GPR18 is required for a normal CD8αα intestinal intraepithelial lymphocyte compartment Xiaoming Wang, Hayakazu Sumida, and Jason G. Cyster 2361 Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants Florian Klein, Lilian Nogueira, Yoshiaki Nishimura, Ganesh Phad, Anthony P. West Jr., Ariel Halper-Stromberg, Joshua A. Horwitz, Anna Gazumyan, Cassie Liu, Thomas R. Eisenreich, Clara Lehmann, Gerd Fätkenheuer, Constance Williams, Masashi Shingai, Malcolm A. Martin, Pamela J. Bjorkman, Michael S. Seaman, Susan Zolla-Pazner, Gunilla B. Karlsson Hedestam, and Michel C. Nussenzweig Articles 2373 Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice Annie Mirsoian, Myriam N. Bouchlaka, Gail D. Sckisel, Mingyi Chen, Chien-Chun Steven Pai, Emanuel Maverakis, Richard G. Spencer, Kenneth W. Fishbein, Sana Siddiqui, Arta M. Monjazeb, Bronwen Martin, Stuart Maudsley, Charles Hesdorffer, Luigi Ferrucci, Dan L. Longo, Bruce R. Blazar, Robert H. Wiltrout, Dennis D. Taub, and William J. Murphy ON THE COVER Mirsoian et al. demonstrate that systemic administration of immunotherapy in mice with increased body fat causes a lethal inflammatory response. Image depicts a backdrop of adipose tissue (pink) with immune cells secreting cytokines (blue). Artwork by Emilie Clark (Emilie@ emilieclark.com). See page 2373 2385 An inherited mutation in NLRC4 causes autoinflammation in human and mice Akiko Kitamura, Yuki Sasaki, Takaya Abe, Hirotsugu Kano, and Koji Yasutomo 2397 Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell–dependent inflammation Jian Wang, Fengqi Li, Haiming Wei, Zhe-Xiong Lian, Rui Sun, and Zhigang Tian 2411 Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence Jordi Guiu, Dylan J.M. Bergen, Emma De Pater, Abul B.M.M.K. Islam, Verónica Ayllón, Leonor Gama-Norton, Cristina Ruiz-Herguido, Jessica González, Nuria López-Bigas, Pablo Menendez, Elaine Dzierzak, Lluis Espinosa, and Anna Bigas 2425 Sex steroid blockade enhances thymopoiesis by modulating Notch signaling See page 2341 Limitation of immune tolerance–inducing thymic epithelial cell development by Spi-B–mediated negative feedback regulation Nobuko Akiyama, Miho Shinzawa, Maki Miyauchi, Hiromi Yanai, Ryosuke Tateishi, Yusuke Shimo, Daisuke Ohshima, Koichi Matsuo, Izumi Sasaki, Katsuaki Hoshino, Guoying Wu, Shintaro Yagi, Jun-ichiro Inoue, Tsuneyasu Kaisho, and Taishin Akiyama 2439 Cytosolic carboxypeptidase CCP6 is required for megakaryopoiesis by modulating Mad2 polyglutamylation Buqing Ye, Chong Li, Zhao Yang, Yanying Wang, Junfeng Hao, Li Wang, Yi Li, Ying Du, Lu Hao, Benyu Liu, Shuo Wang, Pengyan Xia, Guanling Huang, Lei Sun, Yong Tian, and Zusen Fan 2455 Antigen-specific expansion and differentiation of natural killer cells by alloantigen stimulation Tsukasa Nabekura and Lewis L. Lanier 2467 Hrd1-mediated BLIMP-1 ubiquitination promotes dendritic cell MHCII expression for CD4 T cell priming during inflammation Heeyoung Yang, Quan Qiu, Beixue Gao, Sinyi Kong, Zhenghong Lin, and Deyu Fang GPR18 is required for a normal CD8αα intestinal intraepithelial lymphocyte compartment See page 2351