Advances in Experimental Medicine and Biology 941 Xiaojing Ma Editor Regulation of Cytokine Gene Expression in Immunity and Diseases Advances in Experimental Medicine and Biology Volume 941 Editorial Board IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel N.S. ABEL LAJTHA, Kline Institute for Psychiatric Research, Orangeburg, NY, USA JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA RODOLFO PAOLETTI, University of Milan, Milan, Italy More information about this series at http://www.springer.com/series/5584 Xiaojing Ma Editor Regulation of Cytokine Gene Expression in Immunity and Diseases Editor Xiaojing Ma State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Science and Biotechnology Shanghai Jiaotong University, Shanghai , China Department of Microbiology and Immunology Weill Cornell Medical College NY , USA ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-94-024-0919-2 ISBN 978-94-024-0921-5 (eBook) DOI 10.1007/978-94-024-0921-5 Library of Congress Control Number: 2016955715 © Springer Science+Business Media Dordrecht 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer Science+Business Media B.V. Dordrecht Contents 1 Regulation of IFN-γ Expression ............................................................. 1 John Fenimore and Howard A. Young 2 The Interleukin-1 Family ....................................................................... 21 Amir S. Yazdi and Kamran Ghoreschi 3 Regulation of IL-4 Expression in Immunity and Diseases .................. 31 I-Cheng Ho and Shi-Chuen Miaw 4 Regulation of IL-6 in Immunity and Diseases ...................................... 79 Toshio Tanaka , Masashi Narazaki , Kazuya Masuda , and Tadamitsu Kishimoto 5 Regulation of Interleukin-10 Expression .............................................. 89 Sascha Rutz and Wenjun Ouyang 6 Regulation of Interleukin-12 Production in Antigen-Presenting Cells .................................................................... 117 Hua Zheng , Yi Ban , Fang Wei , and Xiaojing Ma 7 Regulation of Interleukin-17 Production .............................................. 139 Wenjuan Dong and Xiaojing Ma 8 Regulation of Interleukin-23 Expression in Health and Disease .............................................................................................. 167 Iain Welsby and Stanislas Goriely 9 Regulation and Immune Function of IL-27 .......................................... 191 Qinghong Wang and Jianguo Liu 10 The Immunobiology of Interleukin-35 and Its Regulation and Gene Expression .............................................................................. 213 Mei Song and Xiaojing Ma v Contributors Yi Ban Department of Microbiology and Immunology , Weill Cornell Medical College , New York , NY , USA Wenjuan Dong Department of Microbiology and Immunology , Weill Cornell Medical College , New York , NY , USA John Fenimore National Cancer Institute at Frederick, Cancer and Infl ammation Program, Center for Cancer Research , NIH , Frederick , MD , USA Kamran Ghoreschi Department of Dermatology , University of Tuebingen , Tuebingen , Germany Stanislas Goriely WELBIO and Institute for Medical Immunology (IMI) , Université Libre de Bruxelles , Charleroi , Belgium I-Cheng Ho Brigham and Women’s Hospital , Harvard Medical School , Boston , MA , USA Tadamitsu Kishimoto Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center , Osaka University , Osaka , Japan Jianguo Liu Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine , Saint Louis University School of Medicine , St. Louis , MO , USA Xiaojing Ma State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Science and Biotechnology , Shanghai Jiaotong University , Shanghai , China Department of Microbiology and Immunology , Weill Cornell Medical College , New York , NY , USA Kazuya Masuda Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center , Osaka University , Osaka , Japan vii viii Contributors Shi-Chuen Miaw College of Medicine, National Taiwan University , Taipei , Taiwan Masashi Narazaki Department of Respiratory Medicine, Allergy and Rheumatic Diseases , Osaka University Graduate School of Medicine, Osaka University , Osaka , Japan Wenjun Ouyang Department of Immunology , Genentech , South San Francisco , CA , USA Present Affi liation: Department of Infl ammation and Oncology , Amgen , South San Francisco, CA , USA Sascha Rutz Department of Cancer Immunology , Genentech , South San Francisco , CA , USA Mei Song Department of Microbiology and Immunology , Weill Cornell Medical College , New York , NY , USA Toshio Tanaka Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine , Osaka University , Osaka , Japan Qinghong Wang Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine , Saint Louis University School of Medicine , St. Louis , MO , USA Fang Wei State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Science and Biotechnology , Shanghai Jiaotong University , Shanghai , China Iain Welsby WELBIO and Institute for Medical Immunology (IMI) , Université Libre de Bruxelles , Charleroi , Belgium Amir S. Yazdi Department of Dermatology , University of Tuebingen , Tuebingen , Germany Howard A. Young National Cancer Institute at Frederick, Cancer and Infl ammation Program, Center for Cancer Research , NIH , Frederick , MD , USA Hua Zheng State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Science and Biotechnology , Shanghai Jiaotong University , Shanghai , China Chapter 1 Regulation of IFN-γ Expression John Fenimore and Howard A. Young Abstract Interferon gamma, referred to here as IFN-γ , is a major component in immunological cell signaling and is a critical regulatory protein for overall immune system function. First discovered in 1965 (Wheelock Science 149: (3681)310–311, 1965), IFN- γ is the only Type II interferon identifi ed. Its expression is both posi- tively and negatively controlled by different factors. In this chapter, we will review the transcriptional and post-transcriptional control of IFN-γ expression. In the tran- scriptional control part, the regular activators and suppressors are summarized, we will also focus on the epigenetic control, such as chromosome access, DNA meth- ylation, and histone acetylation. The more we learn about the control of this regula- tory protein will allow us to apply this knowledge in the future to effectively manipulate IFN- γ expression for the treatment of infections, cancer, infl ammation, and autoimmune diseases. Keywords IFN- γ • Transcriptional control • Epigenetic control • LncRNA • MicroRNA • Activator • Suppressor 1.1 Introduction Interferon gamma, referred to here as IFN-γ , is a major component in immunologi- cal cell signaling and is a critical regulatory protein for overall immune system function. First discovered in 1965 [ 1 ], IFN-γ is the only Type II interferon identi- fi ed. Functionally it is a homodimer with an antiparallel interlocking structure, lack- ing beta sheets but possessing six alpha helixes per monomer. In humans the IFN-γ gene is found on chromosome 12q15 [ 2] and in mice on chromosome 10D2 [ 3 ]. The human gene for IFN-γ has four exon regions and three intron regions, covering 4.04 kbps [ 4]. The receptor complex for IFN-γ, IFNGR1 and IFNGR2, is almost J. Fenimore (*) • H. A. Young National Cancer Institute at Frederick , Cancer and Infl ammation Program, Center for Cancer Research , Frederick , MD 21702 , USA e-mail: [email protected] © Springer Science+Business Media Dordrecht 2016 1 X. Ma (ed.), Regulation of Cytokine Gene Expression in Immunity and Diseases, Advances in Experimental Medicine and Biology 941, DOI 10.1007/978-94-024-0921-5_1 2 J. Fenimore and H.A. Young ubiquitous in all mammalian cells, save erythrocytes. In addition, the structure of IFN-γ is much conserved in studied jawed vertebrates [ 5 ]. IFN-γ’s effects on cells are notable, having been shown to modulate the expres- sion of over 2,300 human genes [ 6 ]. While of the functions of different interferons