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1. Identification of Fibroinflammatory and Fibrotic Transcriptomic Subsets of Human Cutaneous Sclerotic Chronic Graft-Versus-Host Disease

Author

Rachel K. Rosenstein, Jeremy J. Rose, Stephen R. Brooks, Wanxia L. Tsai, Massimo Gadina, Steven Z. Pavletic, Keisuke Nagao, and Edward W. Cowen

Subjects
Dermatology, RL1-803
Abstract

Cutaneous sclerotic chronic graft-versus-host disease (cGVHD) is a common and highly morbid complication of allogeneic hematopoietic stem cell transplantation. Our goals were to identify signals active in the skin of patients with sclerotic cGVHD in an effort to better understand how to treat this manifestation and to explore the heterogeneity of the disease. We identified genes that are significantly upregulated in the skin of patients with sclerotic cGVHD (n = 17) compared with those in the skin of patients who underwent allogeneic hematopoietic stem cell transplantation without cutaneous cGVHD (n = 9) by bulk RNA sequencing. Sclerotic cGVHD was most associated with T helper 1, phagocytic, and fibrotic pathways. In addition, different transcriptomic groups of affected patients were discovered: those with fibrotic and inflammatory/T helper 1 gene expression (the fibroinflammatory group) and those with predominantly fibrotic/TGFβ-associated expression (the fibrotic group). Further study will help elucidate whether these gene expression findings can be used to tailor treatment decisions. Multiple proteins encoded by highly induced genes in the skin (SFRP4, SERPINE2, COMP) were also highly induced in the plasma of patients with sclerotic cGVHD (n = 16) compared with those in plasma of control patients who underwent allogeneic hematopoietic stem cell transplantation without sclerotic cGVHD (n = 17), suggesting these TGFβ and Wnt pathway mediators as candidate blood biomarkers of the disease.

Published
2024
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4. Protein Kinase Antagonists in Therapy of Immunological and Inflammatory Diseases

Author

Arian Laurence, Massimo Gadina, and John J. O'Shea

Subjects
Severe combined immunodeficiency, medicine.anatomical_structure, Immune system, Kinase, Mutant protein, Cell, medicine, Cancer research, Protein phosphorylation, Biology, Signal transduction, medicine.disease, Protein kinase A
Abstract

Reversible protein phosphorylation is a critical regulator of homeostasis in all eukaryotic cells. It is a major means for transmitting information from outside the cell and between the subcellular components within the cell. The importance of protein phosphorylation is illustrated both in cancer, in which mutant protein kinases function as oncogenes, and in disorders of the immune system, where inherited deficiencies of protein kinase signaling are responsible for the majority of cases of severe combined immunodeficiency. On the basis of these findings, targeting protein kinases has been proposed to be a useful strategy in the development of novel immunosuppressant drugs and is one of the most active areas of pharmaceutical drug development, with much of the impetus coming from oncology. This chapter will describe many of the key signaling pathways in immune cells and highlight attempts to design specific inhibitors of key kinases within each pathway to design drugs that limit discrete components of the immune system responsible for particular autoimmune diseases while preserving defense against infections.

Published
2019
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5. List of Contributors

Author

Roshini Sarah Abraham, Cristina Albanesi, Ilias Alevizos, Juan Anguita, Brendan Antiochos, Cynthia Aranow, John P. Atkinson, Howard A. Austin, Subash Babu, Mark C. Ballow, James E. Balow, John W. Belmont, Claudia Berek, Timothy Beukelman, Tapan Bhavsar, J. Andrew Bird, Sarah E. Blutt, Mark Boguniewicz, Rafael Bonamichi-Santos, Bertrand Boisson, Elena Borzova, Prosper N. Boyaka, Joshua Boyce, Sarah K. Browne, Wesley Burks, Jacinta Bustamante, Virginia L. Calder, Matthew Campbell, Adela Rambi G. Cardones, Jean-Laurent Casanova, Mariana Castells, Lisa A. Cavacini, Edwin S.L. Chan, David D. Chaplin, W. Winn Chatham, Edward S. Chen, Javier Chinen, Lisa Christopher-Stine, Michael Ciancanelli, Andrew P. Cope, David B. Corry, Filippo Crea, Randy Q. Cron, Jennifer M. Cuellar-Rodriguez, Marinos C. Dalakas, Sara M. Dann, Betty Diamond, Terry W. Du, Stéphanie Dupuis-Boisson, Todd N. Eagar, Craig A. Elmets, Doruk Erkan, Laura Fanning, Erol Fikrig, Davide Flego, Thomas A. Fleisher, Luz Fonacier, Andrew P. Fontenot, Alexandra F. Freeman, Anthony J. Frew, Kohtaro Fujihashi, Massimo Gadina, Moshe E. Gatt, M. Eric Gershwin, Susan L. Gillespie, Jörg J. Goronzy, Sangeeta Goswami, Clive E.H. Grattan, Neil S. Greenspan, Sarthak Gupta, Claire E. Gustafson, Russell P. Hall, Robert G. Hamilton, Laurie E. Harrington, Leonard C. Harrison, Sarfaraz A. Hasni, Arthur Helbling, Joanna Hester, Steven M. Holland, Dennis Hourcade, Nicholas D. Huntington, Tracy Hwangpo, John B. Imboden, Fadi Issa, Shai Izraeli, Elaine S. Jaffe, Sirpa Jalkanen, Stacie Jones, Emmanuelle Jouanguy, Sarah Kabbani, Stefan H.E. Kaufmann, Farrah Kheradmand, Donald B. Kohn, Robert Korngold, Anna Kovalszki, Douglas B. Kuhns, Hrishikesh Kulkarni, Caroline Y. Kuo, Arash Lahouti, C. Ola Landgren, Arian Laurence, Joyce S. Lee, Catherine Lemière, Donald Y.M. Leung, Arnold I. Levinson, Ofer Levy, Dorothy E. Lewis, Phoebe Lin, Andreas Linkermann, Giovanna Liuzzo, Michael D. Lockshin, Allison K. Lord, Jay N. Lozier, Amber Luong, Raashid Luqmani, Meggan Mackay, Jonathan S. Maltzman, Peter J. Mannon, Michael P. Manns, James G. Martin, Craig L. Maynard, Samual McCash, Douglas R. McDonald, Peter C. Melby, Stephen D. Miller, Anna L. Mitchell, Amirah Mohd-Zaki, Carolyn Mold, David R. Moller, Dimitrios S. Monos, Scott N. Mueller, Catharina M. Mulders-Manders, Mark J. Mulligan, Ulrich R. Müller, Pashna N. Munshi, Kazunori Murata, Philip M. Murphy, Nicolás Navasa, Pierre Noel, Luigi D. Notarangelo, Robert L. Nussbaum, Thomas B. Nutman, Stephen L. Nutt, João B. Oliveira, Thomas L. Ortel, John J. O'Shea, Sung-Yun Pai, Lavannya Pandit, Mary E. Paul, Simon H.S. Pearce, Daniela Pedicino, Erik J. Peterson, Capucine Picard, Stefania Pittaluga, Debra Long Priel, Jennifer Puck, Anne Puel, Andreas Radbruch, Stephen T. Reece, John D. Reveille, Robert R. Rich, Chaim M. Roifman, Antony Rosen, James T. Rosenbaum, Sergio D. Rosenzweig, Barry T. Rouse, Scott D. Rowley, Shimon Sakaguchi, Marko Salmi, Andrea J. Sant, Sarah W. Satola, Valerie Saw, Marcos C. Schechter, Harry W. Schroeder, Benjamin M. Segal, Carlo Selmi, Sushma Shankar, Anu Sharma, Padmanee Sharma, William T. Shearer, Richard M. Siegel, Anna Simon, Gideon P. Smith, David S. Stephens, Robin Stephens, Alex Straumann, Leyla Y. Teos, Laura Timares, Wulf Tonnus, Raul M. Torres, Gülbü Uzel, Jeroen C.H. van der Hilst, Jos W.M. van der Meer, John Varga, Jatin M. Vyas, Meryl Waldman, Peter Weiser, Peter F. Weller, Cornelia M. Weyand, Fredrick M. Wigley, Robert J. Winchester, James B. Wing, Kathryn J. Wood, Xiaobo Wu, Hui Xu, Cassian Yee, and Shen-Ying Zhang

Published
2019
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6. Contributors

Author

Engy Abdellatif, Aryeh M. Abeles, Abby G. Abelson, Abhishek Abhishek, Steven B. Abramson, Jonathan D. Adachi, Michael A. Adams, Thomas Aigner, Shizuo Akira, Daniel Aletaha, Antonios O. Aliprantis, Adriana Almeida de Jesus, Roy D. Altman, Mary-Carmen Amigo, Martin Aringer, Dana P. Ascherman, Shervin Assassi, Sergei P. Atamas, Pedro Ming Azevedo, Alan N. Baer, Dominique Baeten, Colin Baines, Nancy A. Baker, Emese Balogh, Alejandro Balsa, Xenofon Baraliakos, Thomas Bardin, Les Barnsley, Joan M. Bathon, Angela Bauch, Jill J.F. Belch, Nicholas Bellamy, Teresita Bellido, Michael Benjamin, Michael W. Beresford, Brian Berman, Bonnie Lee Bermas, George Bertsias, John P. Bilezikian, Yelda Bilginer, Julius Birnbaum, Felicity L. Bishop, Jane F. Bleasel, Markus Böhm, Marcy B. Bolster, Stefano Bombardieri, Michael Bonelli, Sydney L. Bonnick, Dimitrios T. Boumpas, Aline Bozec, Richard D. Brasington, Juergen Braun, Matthew A. Brown, Ian N. Bruce, William D. Bugbee, Marwan A.S. Bukhari, Rubén Burgos-Vargas, Gerd-Rüdiger Burmester, Jane C. Burns, David B. Burr, Frank Buttgereit, Vivian P. Bykerk, Leonard H. Calabrese, Jeffrey P. Callen, Sabrina Cavallo, Tim E. Cawston, Vinod Chandran, Michael Denis Chard, Prateek Chaudhary, Lan X. Chen, Hyon K. Choi, Ernest H. Choy, Lisa Christopher-Stine, Alvina D. Chu, Daniel J. Clauw, Philip J. Clements, Megan E.B. Clowse, J. Gerry Coghlan, Philip G. Conaghan, Cyrus Cooper, Karen H. Costenbader, Paul Creamer, José C. Crispín, Bruce N. Cronstein, Raymond Cross, Natalie E. Cusano, Maurizio Cutolo, Chris D'Adamo, Vivette D'Agati, David P. D'Cruz, Hanne Dagfinrud, David I. Daikh, Nicola Dalbeth, Seamus E. Dalton, Shouvik Dass, Aileen M. Davis, Karel De Ceulaer, Chad L. Deal, Kevin D. Deane, Alessandra Della Rossa, Paul F. Dellaripa, Elaine Dennison, Christopher P. Denton, Paul Dieppe, Michael Doherty, Patricia Dolan, Rachelle Donn, Olga Dvorkina, George S.M. Dyer, Richard Eastell, N. Lawrence Edwards, Paul Emery, Gurhan Erturan, Luis R. Espinoza, Steve Eyre, Antonios C. Fanouriakis, Joshua Farber, Shawn Farrokhi, Anders Fasth, Eugen Feist, Debbie Feldman, David T. Felson, John D. Fisk, G. Kelley Fitzgerald, Raymond H. Flores, David A. Fox, Clair A. Francomano, Jennifer Frangos, Anthony J. Freemont, Kevin B. Fricka, Daniel E. Furst, Cem Gabay, Massimo Gadina, J.S. Hill Gaston, Steffen Gay, Lianne S. Gensler, Laura Geraldino-Pardilla, Danielle M. Gerlag, Ellen M. Ginzler, Alison M. Gizinski, Dafna D. Gladman, Garry E. Gold, Raphaela Goldbach-Mansky, Sarah Goldingay, Sharon M. Gordon, Rachel Gorodkin, Jörg J. Goronzy, Simon Görtz, Rodney Grahame, Andrew J. Grainger, Ellen M. Gravallese, Jeffrey D. Greenberg, Bansari Gujar, Matilda Hagan, Karlene Hagley, Alan J. Hakim, John C. Hall, Vedat Hamuryudan, John G. Hanly, Eric P. Hanson, Boulos Haraoui, John B. Harley, Philip J. Hashkes, Gillian A. Hawker, Philip N. Hawkins, Turid Heiberg, Dick Heinegård, Simon M. Helfgott, Pauline Y.P. Ho, Marc C. Hochberg, Jacqueline Hochman, Chelsea J. Hodgkiss-Harlow, Robert W. Hoffman, Markus Hoffmann, V. Michael Holers, Michael F. Holick, Christopher Holroyd, Osvaldo Hübscher, David J. Hunter, M. Elaine Husni, Robert D. Inman, Zacharia Isaac, Maura D. Iversen, Douglas A. Jabs, William Jackson, Sarada Jaimungal, Judith A. James, Rose-Marie Javier, Alyssa K. Johnsen, Joanne M. Jordan, Tsuneyasu Kaisho, Cees G.M. Kallenberg, David Kane, Mohit Kapoor, Elizabeth W. Karlson, Dimitrios G. Kassimos, Daniel L. Kastner, Jeffrey N. Katz, Jonathan Kay, Jennifer A. Kelly, Edward Keystone, Munther A. Khamashta, Dinesh Khanna, Ingvild Kjeken, Alisa E. Koch, Matthew F. Koff, Leah Kottyan, Loukia A. Koutsogeorgopoulou, Virginia Byers Kraus, Pradeep Kumar, Tore K. Kvien, Robert Lafyatis, Robert B.M. Landewé, Carol A. Langford, Arthur N. Lau, Ronald M. Laxer, Thomas J. Learch, George Lewith, Yi Li, Katherine P. Liao, Geoffrey Littlejohn, Pilar Lorenzo, Thomas A. Luger, Ingrid E. Lundberg, Karin Lundberg, Klaus P. Machold, C. Ronald MacKenzie, Alfred D. Mahr, Eric Manheimer, Joan C. Marini, Javier Marquez, Debbie Marsden, Johanne Martel-Pelletier, Emilio Martín-Mola, Manuel Martínez-Lavín, Elena M. Massarotti, Eric L. Matteson, Stephen J. Matzat, Reza Mayahi, Maureen Davidica Mayes, Timothy McAlindon, Hayley McBain, Bill McCarberg, Edward F. McCarthy, Geraldine McCarthy, Michael F. McDermott, Dennis McGonagle, Lachy McLean, Peter A. Merkel, Jamal A. Mikdashi, Frederick W. Miller, Paul D. Miller, Kirsten Minden, Paul A. Monach, Kathleen Mulligan, Gauthier Namur, Esperanza Naredo, Kim E. Naylor, Amanda E. Nelson, Stanton P. Newman, Ellen Nordal, Ulrich Nöth, Eleana Ntatsaki, John J. O'Shea, Chester V. Oddis, Alejandro Olivé, Mohammed A. Omair, Michael J. Ombrello, Antonina Omisade, Voon H. Ong, Patrik Önnerfjord, Philippe Orcel, Caroline Ospelt, Seza Ozen, Stephen A. Paget, Dipak R. Patel, Carlo Patrono, Jean-Pierre Pelletier, Rosa Maria Rodrigues Pereira, Clarissa A. Pilkington, Michael H. Pillinger, Carlos Pineda, Robert M. Plenge, Andrew Price, Luminita Pricop, Lars Rackwitz, Angelo Ravelli, Anthony C. Redmond, Westley H. Reeves, Elaine F. Remmers, Luis Requena, Clio Ribbens, Bruce C. Richardson, Elena Riera Alonso, Graham Riley, Christopher Ritchlin, Susan Y. Ritter, Ivan O. Rosas, Drew D. Rowan, Martin Rudwaleit, Marina Rull, Marite Rygg, Kenneth G. Saag, Jane E. Salmon, Donald M. Salter, Daniel J. Salzberg, Philip N. Sambrook, Tore Saxne, Hans-Georg Schaible, Jose U. Scher, Georg Schett, Nicole Schmitz, Benjamin Schreiber, H. Ralph Schumacher, Daniella Muallem Schwartz, David G.I. Scott, Margaret Seton, Lauren M. Shapiro, Nancy Sharby, Jeffrey Siegel, Richard M. Siegel, Joachim Sieper, Richard M. Silver, Shonni J. Silverberg, Julia F. Simard, Barry P. Simmons, Robert W. Simms, Nora G. Singer, Malcolm D. Smith, Stacy E. Smith, Josef S. Smolen, Tim D. Spector, Virginia D. Steen, Allen C. Steere, Günter Steiner, Andre F. Steinert, George Stojan, John H. Stone, Vibeke Strand, Rainer H. Straub, Elizabeth A. Streeten, Giulio Superti-Furga, Deborah P.M. Symmons, Zoltan Szekanecz, Paul P. Tak, Antonio Tavoni, Peter C. Taylor, Robert Terkeltaub, Sarah S. Thomas, Jennifer E. Thorne, Jonathan H. Tobias, Adriana H. Tremoulet, George C. Tsokos, Rocky S. Tuan, Carl Turesson, Sebastian H. Unizony, Ana M. Valdes, Wim B. van den Berg, Désirée van der Heijde, Ronald Frits van Vollenhoven, John Varga, Dimitrios Vassilopoulos, Edward M. Vital, Karen Walker-Bone, Daniel J. Wallace, Gary Warburton, Robert J. Ward, Richard Watts, Mihir D. Wechalekar, Lucy R. Wedderburn, Michael E. Weinblatt, Matthew R. Weir, Claire Y.J. Wenham, Sterling G. West, Cornelia M. Weyand, Kenneth E. White, Kevin L. Winthrop, John B. Wong, Anthony D. Woolf, Jane Worthington, Huji Xu, Hasan Yazici, D.A. Young, Sebahattin Yurdakul, Yuqing Zhang, and Haoyang Zhuang

Published
2015
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7. Cytokines

Author

John J. O'Shea, Massimo Gadina, Richard M. Siegel, and Joshua Farber

Published
2015
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8. Cytokines and cytokine receptors

Author

John J. O'Shea, Richard M. Siegel, and Massimo Gadina

Subjects
Suppressor of cytokine signaling 1, business.industry, medicine.medical_treatment, fungi, food and beverages, Biology, Proinflammatory cytokine, Cell biology, Immune system, Cytokine, Interleukin 25, Immunology, Medicine, Signal transduction, business, Receptor, Common gamma chain
Abstract

Cytokines are critical mediators of communication for the immune system, and they are essential for host defense against pathogens. Cytokines can be secreted by immune cells but can also be produced by a wide variety of cells in response to infection, as with interferons, or can be produced or released from cells in response to cellular damage when cell integrity is compromised. Acting through a number of conserved signaling pathways that modulate cellular metabolism and transcriptional programming, cytokines control many aspects of cellular growth, development, and survival and can also reprogram cells in the local tissue environment to enhance certain types of immune responses. Many primary immunodeficiency syndromes are caused by germline mutations in cytokines, cytokine receptors, or signal transduction mediators. Autoimmune and inflammatory diseases can result from excess cytokine production or responsiveness. As key mediators of disease, cytokines, their receptors, and signal transduction pathways have emerged as key targets for therapeutic monoclonal antibodies and small molecules.

Published
2013
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9. List of contributors

Author

Roshini Sarah Abraham, Cristina Albanesi, Ilias Alevizos, Juan Anguita, Gregory M. Anstead, Cynthia Aranow, Howard A. Austin, Subash Babu, Mark C. Ballow, James E. Balow, David R. Barnidge, John W. Belmont, Gabrielle T. Belz, Dina Ben-Yehuda, Claudia Berek, Timothy Beukelman, Thomas Bieber, Johannes W.J. Bijlsma, Jack J.H. Bleesing, Sarah E. Blutt, Barbara Bohle, Elena Borzova, Prosper N. Boyaka, Brockow Knut, Jacinta Bustamante, Frank Buttgereit, Mary Byrne, Virginia L. Calder, Magda Carneiro-Sampaio, Sebastian Carotta, Jean-Laurent Casanova, Lisa A. Cavacini, Edwin S.L. Chan, Javier Chinen, Tanuja Chitnis, Monique Cho, Lisa Christopher-Stine, Andrew P. Cope, David B. Corry, Tricia Cottrell, Antonio Coutinho, Marco Craveiro, Randy Q. Cron, Jennifer Cuellar-Rodriguez, Marinos C. Dalakas, Stephanie C. de Barros, Blythe H. Devlin, Betty Diamond, Angela Dispenzieri, Terry W. Du Clos, Stéphanie Dupuis-Boisson, Todd N. Eagar, Kim D. Edhegard, George S. Eisenbarth, Craig A. Elmets, Doruk Erkan, Mark B. Feinberg, Erol Fikrig, Thomas A. Fleisher, Andrew P. Fontenot, Luis M. Franco, Alexandra F. Freeman, Anthony J. Frew, Thea Friedman, Kohtaro Fujihashi, Massimo Gadina, Stephen J. Galli, H. Bobby Gaspar, Moshe E. Gatt, M. Eric Gershwin, Kamran Ghoreschi, Susan L. Gillespie, Jörg J. Goronzy, Clive E.H. Grattan, Neil S. Greenspan, Eyal Grunebaum, Gabrielle Haeberli, Russell P. Hall, Robert G. Hamilton, Gregory R. Harriman, Sarfaraz A. Hasni, Arthur Helbling, Melanie Hingorani, Steven M. Holland, Petr L. Hruz, Gabor Illei, John B. Imboden, Shai Izraeli, Elaine S. Jaffe, Caroline Jagobi, Sirpa Jalkanen, Pim Jetanalin, Emmanuelle Jouanguy, Carl H. June, Axel Kallies, Stefan H.E. Kaufmann, Arthur Kavanaugh, Sabiha Khan, Farrah Kheradmand, Samia J. Khoury, Gary A. Koretzky, Robert Korngold, Anna Kovalszki, Douglas B. Kuhns, Robert A. Kyle, Ian R. Lanza, Arian Laurence, Susan J. Lee, Michael J. Lenardo, Arnold I. Levinson, Ofer Levy, David B. Lewis, Dorothy E. Lewis, Sue L. Lightman, Michael D. Lockshin, Michael T. Lotze, Amber Luong, Meggan Mackay, Jean-Luc Malo, Jonathan S. Maltzman, Peter J. Mannon, Michael P. Manns, Mary Louise Markert, Elizabeth A. McCarthy, Douglas R. McDonald, Jerry R. McGhee, Peter C. Melby, Dean D. Metcalfe, Martin Metz, Stephen D. Miller, Anna L. Mitchell, Shruti Mittal, Makoto Miyara, Carolyn Mold, David R. Moller, Scott N. Mueller, Ulrich R. Müller, Philip M. Murphy, Pierre Noel, Luigi Notarangelo, Thomas B. Nutman, Stephen L. Nutt, João B. Oliveira, Chris M. Olson, John J. O'Shea, Sung-Yun Pai, Lavannya Pandit, Mary E. Paul, Simon H.S. Pearce, Erik J. Peterson, Capucine Picard, Werner J. Pichler, Stefania Pittaluga, Anne Puel, Andreas Radbruch, Stephen T. Reece, John D. Reveille, Robert R. Rich, Christine Rivat, Bruce W.S. Robinson, John R. Rodgers, Chaim M. Roifman, Antony Rosen, James T. Rosenbaum, Barry T. Rouse, Scott D. Rowley, Shimon Sakaguchi, Marko Salmi, Harry W. Schroeder, Markus J.H. Seibel, Carlo Selmi, William M. Shafer, Prediman K. Shah, Sushma Shankar, Alan R. Shaw, William T. Shearer, Javed Sheikh, Richard Siegel, Anna Simon, Philip L. Simonian, Gideon P. Smith, Justine R. Smith, Andrew L. Snow, David S. Stephens, John H. Stone, Alex Straumann, Helen C. Su, Louise Swainson, Ewa Szymanska-Mroczek, Naomi Taylor, Adrian J. Thrasher, Laura Timares, Raul M. Torres, Gülbŭ Uzel, Jos W.M. van der Meer, Jeroen C.H. van der Hilst, John Varga, Meryl Waldman, Peter Weiser, Peter F. Weller, Cornelia M. Weyand, Theresa L. Whiteside, Fredrick M. Wigley, Robert J. Winchester, Kajsa Wing, Kathryn Wood, Hui Xu, Shen-Ying Zhang, and Valérie S. Zimmermann

Published
2013
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10. The Newest Interleukins: Recent Additions to the Ever‐Growing Cytokine Family

Author

Massimo Gadina, Qian Chen, and Helen P. Carroll

Subjects
Allergy, medicine.medical_treatment, Regulator, Interleukin, T helper cell, Biology, medicine.disease_cause, medicine.disease, Autoimmunity, Cytokine, medicine.anatomical_structure, Immune system, Immunology, medicine, Receptor
Abstract

Cytokines play a critical role in the control of the innate and adaptive immune responses. The most recent additions to the ever‐growing family of cytokines include interleukin (IL)‐27, IL‐28A, IL‐28B, IL‐29, IL‐31, IL‐32, and IL‐33. Many of the newly identified cytokines and/or their specific receptors have been identified using bioinformatics. The coming of age of this discipline has coincided with completion of the sequencing of the human genome thus enabling the identification of new uncharacterized proteins. The latest additions to the interleukin family have shed new light on the intricacies of immune system regulation. These novel cytokines have pleiotrophic actions ranging from antiviral immunity to the regulation of Th2 immune responses. For example, the discovery of IL‐27 has greatly improved our understanding of the factors regulating the polarization of the T helper cell responses and IL‐31 appears to be an important regulator of Th2 responses. On the other hand, IL‐28 and IL‐29 are considered to be critical for mounting an efficient antiviral response and IL‐32 and IL‐33, which are yet to be fully characterized, are emerging as important components of the inflammatory response in allergy and autoimmunity. These new cytokine/receptor combinations may therefore serve as novel targets for the treatment and control of allergy, autoimmune diseases, and some cancers.

Published
2006
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