SPECIAL IMMUNOLOGY [ EDITION ] aaas.org/science-journals WE ARE YOUR ONE STOP SHOP FOR IMMUNOLOGY THOUSANDS OF PRODUCTS Antibodies ·Immunoassays ·Proteins ·SmallMolecules FROM TRUSTEDSUPPLIERS www.sapphire-usa.com Mimic True Activity MEGACD40L® Protein for Immune Response Activation High-Activity, High-Purity Protein for Co-Stimulating Activation of an Immune Response MEGACD40L protein is an optimized, oligomeric construct which mimics in vivo membrane-assisted CD40L aggregation and stimulation without the MEGACD40L Protein Results in Greater Activation need for enhancers. Enzo’s expertise in the production of challenging protein complexes, such as MEGACD40L protein, results in a product you can rely on for the duration of your study. •Engages with immune cell receptors and acts as a potent and sustained immunostimulator •Improved stability and enhanced activity, when compared to CD40L, alone or with enhancers •High purity and low endotoxin to eliminate experimental artifacts •Guarantees reliable results through consistent lot-to-lot performance •Widely cited in peer reviewed publications Autoimmunity | Cancer Immunotherapy | Endocrinology | Vaccine Development scientists enabling scientists™ www.enzolifesciences.com/MEGACD40L © 2017 Enzo Life Sciences Science_Enzo_FP_MegaCD40L.indd 1 2/8/17 10:59 AM SPECIAL EDITION: Immunology IN THIS BOOKLET Select research published in Science Immunology, Science Signaling, and Science Translational Medicine Science Immunology This booklet features articles from three journals RESEARCH ARTICLE in the Science family of journals: Science Immu- 4 Myosin light chains 9 and 12 are functional nology, Science Signaling, and Science Transla- ligands for CD69 that regulate airway tional Medicine. The content covers molecular inflammation details of the signaling processes that occur in Koji Hayashizaki et al. (Toshinori Nakayama) cells of both the innate and adaptive immune systems (T cells, B cells, NK cells, macrophages, RESEARCH ARTICLE ABSTRACTS dendritic cells), how inflammation is regulated, 14 ZBP1/DAI is an innate sensor of influenza virus insights into pathophysiological processes and triggering the NLRP3 inflammasome and diseases associated with the immune system, and how to re-educate the programmed cell death pathways immune system or modify immune function for therapeutic benefit. Teneema Kuriakose et al. (Thirumala-Devi Kanneganti) Image: freshidea/AdobeStock.com Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients Thomas Condamine et al. (Dmitry I. Gabrilovic) Science Immunology publishes original, peer-reviewed research articles that report critical advances in all areas of immunological research, in- Science Signaling cluding important new tools and techniques. RESEARCH ARTICLE Chief Scientific Advisors Editor 16 Distinct microenvironmental cues stimulate Abul K. Abbas, M.D. Angela C. Colmone, Ph.D. divergent TLR4-mediated signaling pathways in University of California, San Francisco AAAS, Washington, DC macrophages Anna M. Piccinini et al. (Kim S. Midwood) Federica Sallusto, Ph.D. Editorial Team Università della Svizzera Italiana Anand Balasubramani, Ph.D. RESEARCH ARTICLE ABSTRACTS 32 Bypassing STAT3-mediated inhibition of the transcriptional regulator ID2 improves the antitumor efficacy of dendriticcells Haiyan S. Li et al. (Stephanie S. Watowich) Reactive oxygen species induce virus- Science Signaling publishes peer-reviewed, original research investigating independent MAVS oligomerization in systemic cell signaling that underlies physiology and disease, on the molecular, lupus erythematosus cellular, intercellular and organismal levels. Iwona A. Buskiewicz et al. (Andreas Koenig) Chief Scientific Editor Editorial Team Michael B. Yaffe, M.D., Ph.D. John F. Foley, Ph.D. Massachusetts Institute of Technology Wei Wong, Ph.D. Science Translational Medicine Leslie K. Ferrarelli, Ph.D. Annalisa VanHook, Ph.D. RESEARCH ARTICLE 34 Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia Rizwan Romee et al. (Todd A. Fehniger) Science Translational Medicine is an interdisciplinary journal that pub- RESEARCH ARTICLE ABSTRACTS lishes translational research that matters for human health, filling the 46 Nonprogressing HIV-infected children share knowledge gaps between research and medical application. fundamental immunological features of nonpathogenic SIV infection Chief Scientific Advisors Editor Maximilian Muenchhoff et al. (Philip Goulder) Garret FitzGerald, M.D. Orla M. Smith, Ph.D. University of Pennsylvania AAAS, Washington, DC A divergent population of autoantigen- responsive CD4+ T cells in infants prior to Elazer R. Edelman, M.D., Ph.D. Editorial Team β cell autoimmunity Massachusetts Institute Yevgeniya Nusinovich, M.D., Ph.D. Anne-Kristin Heninge et al. (Ezio Bonifacio) of Technology Caitlin A. Czajka, Ph.D. Lindsey Pujanandez, Ph.D. Learn more and submit your research today: aaas.org/science-journals © 2017 by The American Association for the Advancement of Science. All Rights Reserved. Science Immunology SCIENCE IMMUNOLOGY | RESEARCH ARTICLE RESEARCH ARTICLE ASTHMA 2016 © The Authors, some rights reserved; Myosin light chains 9 and 12 are functional ligands for exclusive licensee American Association CD69 that regulate airway inflammation for the Advancement of Science. Koji Hayashizaki,1* Motoko Y. Kimura,1* Koji Tokoyoda,1,2* Hiroyuki Hosokawa,1 Kenta Shinoda,1 Kiyoshi Hirahara,1 Tomomi Ichikawa,1 Atsushi Onodera,1 Asami Hanazawa,1,2 Chiaki Iwamura,1 Jungo Kakuta,3 Kenzo Muramoto,3 Shinichiro Motohashi,4 Damon J. Tumes,1,5 Tomohisa Iinuma,6 Heizaburo Yamamoto,6 Yuzuru Ikehara,7 Yoshitaka Okamoto,6 Toshinori Nakayama1,8† Recent decades have witnessed a rapid worldwide increase in chronic inflammatory disorders such as asthma. CD4+ T helper 2 cells play critical roles in the pathogenesis of allergic airway inflammation, and CD69 expression on activated CD4 T cells is required to induce allergic inflammation in tissues. However, how CD69 mechanisti- Downloaded from cally controls allergic inflammation remains poorly defined. In lymphoid tissues, CD69 regulates cellular retention through inhibition of S1P1 expression and requires no specific ligands to function. In contrast, we show herein that myosin light chain (Myl) 9 and Myl12 are new functional ligands for CD69. Blockade of CD69-Myl9/12 inter- action ameliorates allergic airway inflammation in ovalbumin-induced and house dust mite–induced mouse models of asthma. Within the inflamed mouse airways, we found that the expression of Myl9/12 was increased and that platelet-derived Myl9/12 localized to the luminal surface of blood vessels and formed intravascular net- http://immunology.sciencemag.org/ like structures. Analysis of nasal polyps of eosinophilic chronic rhinosinusitis patients revealed that Myl9/12 ex- pression was increased in inflammatory lesions and was distributed within net-like structures in the intravascular space. In addition, we detected Myl9/12 in perivascular spaces where many CD69+ cells were positioned within Myl9/12 structures. Thus, CD69-Myl9/12 interaction is a key event in the recruitment of activated CD69+ T cells to inflamed tissues and could be a therapeutic target for intractable airway inflammatory diseases. INTRODUCTION Furthermore, CD69-deficient CD4 T cells failed to generate memory CD69 is a type II transmembrane glycoprotein with C-type lectin do- CD4 T cells and to induce secondary antibody responses because of mains that is expressed on activated leukocytes, especially on T cells their inability to relocate into and persist in the bone marrow (BM), (1, 2). CD69 expression is rapidly induced upon T cell receptor (TCR) where antigen-specific resting memory CD4 T cells are maintained stimulation (3) and is therefore used as a marker for early activation (7, 9). These inflammatory responses were efficiently prevented by in of T cells. CD69 is also expressed on developing T cells undergoing vivo treatment with blocking anti-CD69 antibodies (5, 7, 8), suggest- selection in the thymus (2). Furthermore, several recent studies have ing that CD69 may function through specific interactions with one by guest on February 7, 2017 shown that CD69 plays important roles in establishing tissue inflammation or more ligands expressed in inflamed sites. However, such ligands by promoting cell recruitment and retention in various sites (4–8). CD69 have not yet been determined. regulates cellular retention within lymphoid tissues by inhibiting S1P1 ex- Accumulation of CD69-expressing leukocytes was observed in a pression through direct interaction (4), whereas it remains unknown number of human chronic inflammatory disorders, such as asthma whether there are any specific ligands for CD69 in peripheral tissues. (10) and eosinophilic pneumonia (11). CD69 expression on eosino- We have previously reported that CD69 expression on effector phils is induced by cytokine stimulation, including interleukin-3 CD4 T cells (5, 8) and neutrophils (6) is crucial for the establishment (IL-3), IL-5, granulocyte-macrophage colony-stimulating factor, and of tissue inflammatory responses. For example, CD69-deficient antigen- interferon-g (10, 11), suggesting that cytokines in the inflammatory specific CD4 T cells failed to migrate into and be retained in the lung, environment may induce CD69 expression on effector leukocytes resulting in reduced airway inflammatory responses after antigenic and