Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells
Abstract
Interleukin-12 (IL-12) and IL-23 are heterodimeric cytokines that are produced by antigen-presenting cells to regulate the activation and differentiation of lymphocytes, and they share IL-12Rβ1 as a receptor signaling subunit. In this paper, we present a crystal structure of the quaternary IL-23 (IL-23p19/p40)/IL-23R/IL-12Rβ1 complex, together with cryoelectron microscopy (cryo-EM) maps of the complete IL-12 (IL-12p35/p40)/IL-12Rβ2/IL-12Rβ1 and IL-23 receptor (IL-23R) complexes, which reveal “non-canonical” topologies where IL-12Rβ1 directly engages the common p40 subunit. We targeted the shared IL-12Rβ1/p40 interface to design a panel of IL-12 partial agonists that preserved interferon gamma (IFNγ) induction by CD8+ T cells but impaired cytokine production from natural killer (NK) cells in vitro. These cell-biased properties were recapitulated in vivo, where IL-12 partial agonists elicited anti-tumor immunity to MC-38 murine adenocarcinoma absent the NK-cell-mediated toxicity seen with wild-type IL-12. Thus, the structural mechanism of receptor sharing used by IL-12 family cytokines provides a protein interface blueprint for tuning this cytokine axis for therapeutics.
- Authors:
-
[1];
[1];
[1];
[1];
[1];
[1];
[1];
[1];
- Stanford Univ., CA (United States). School of Medicine
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Mathers Foundation; Ludwig Foundation; National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institute of General Medical Sciences (NIGMS)
- OSTI Identifier:
- 1781662
- Grant/Contract Number:
- AC02-76SF00515; R01-AI51321; DGE-1656518; AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Cell
- Additional Journal Information:
- Journal Volume: 184; Journal Issue: 4; Journal ID: ISSN 0092-8674
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; IL-12; IL-23; immunology; receptor biology; structural biology; signaling
Citation Formats
Glassman, Caleb R., Mathiharan, Yamuna Kalyani, Jude, Kevin M., Su, Leon, Panova, Ouliana, Lupardus, Patrick J., Spangler, Jamie B., Ely, Lauren K., Thomas, Christoph, Skiniotis, Georgios, and Garcia, K. Christopher. Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells. United States: N. p., 2021.
Web. doi:10.1016/j.cell.2021.01.018.
Glassman, Caleb R., Mathiharan, Yamuna Kalyani, Jude, Kevin M., Su, Leon, Panova, Ouliana, Lupardus, Patrick J., Spangler, Jamie B., Ely, Lauren K., Thomas, Christoph, Skiniotis, Georgios, & Garcia, K. Christopher. Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells. United States. https://doi.org/10.1016/j.cell.2021.01.018
Glassman, Caleb R., Mathiharan, Yamuna Kalyani, Jude, Kevin M., Su, Leon, Panova, Ouliana, Lupardus, Patrick J., Spangler, Jamie B., Ely, Lauren K., Thomas, Christoph, Skiniotis, Georgios, and Garcia, K. Christopher. Thu .
"Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells". United States. https://doi.org/10.1016/j.cell.2021.01.018. https://www.osti.gov/servlets/purl/1781662.
@article{osti_1781662,
title = {Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells},
author = {Glassman, Caleb R. and Mathiharan, Yamuna Kalyani and Jude, Kevin M. and Su, Leon and Panova, Ouliana and Lupardus, Patrick J. and Spangler, Jamie B. and Ely, Lauren K. and Thomas, Christoph and Skiniotis, Georgios and Garcia, K. Christopher},
abstractNote = {Interleukin-12 (IL-12) and IL-23 are heterodimeric cytokines that are produced by antigen-presenting cells to regulate the activation and differentiation of lymphocytes, and they share IL-12Rβ1 as a receptor signaling subunit. In this paper, we present a crystal structure of the quaternary IL-23 (IL-23p19/p40)/IL-23R/IL-12Rβ1 complex, together with cryoelectron microscopy (cryo-EM) maps of the complete IL-12 (IL-12p35/p40)/IL-12Rβ2/IL-12Rβ1 and IL-23 receptor (IL-23R) complexes, which reveal “non-canonical” topologies where IL-12Rβ1 directly engages the common p40 subunit. We targeted the shared IL-12Rβ1/p40 interface to design a panel of IL-12 partial agonists that preserved interferon gamma (IFNγ) induction by CD8+ T cells but impaired cytokine production from natural killer (NK) cells in vitro. These cell-biased properties were recapitulated in vivo, where IL-12 partial agonists elicited anti-tumor immunity to MC-38 murine adenocarcinoma absent the NK-cell-mediated toxicity seen with wild-type IL-12. Thus, the structural mechanism of receptor sharing used by IL-12 family cytokines provides a protein interface blueprint for tuning this cytokine axis for therapeutics.},
doi = {10.1016/j.cell.2021.01.018},
journal = {Cell},
number = 4,
volume = 184,
place = {United States},
year = {Thu Feb 18 00:00:00 EST 2021},
month = {Thu Feb 18 00:00:00 EST 2021}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Activation of natural killer cells with interleukin 2 (IL-2) and IL-12 increases perforin binding and subsequent lysis of tumour cells: Activation With IL-2 and IL-12 Increases Perforin Binding
journal, September 2001
- Lehmann, Christof; Zeis, Matthias; Uharek, Lutz
- British Journal of Haematology, Vol. 114, Issue 3
Preactivation with IL-12, IL-15, and IL-18 Induces CD25 and a Functional High-Affinity IL-2 Receptor on Human Cytokine-Induced Memory-like Natural Killer Cells
journal, April 2014
- Leong, Jeffrey W.; Chase, Julie M.; Romee, Rizwan
- Biology of Blood and Marrow Transplantation, Vol. 20, Issue 4
The interleukin-12 subunit p40 specifically inhibits effects of the interleukin-12 heterodimer
journal, September 1993
- Mattner, Frank; Fischer, Susanne; Guckes, Stefanie
- European Journal of Immunology, Vol. 23, Issue 9
IL-12 family cytokines: immunological playmakers
journal, July 2012
- Vignali, Dario A. A.; Kuchroo, Vijay K.
- Nature Immunology, Vol. 13, Issue 8
A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions
journal, August 2020
- Wojtowicz, Woj M.; Vielmetter, Jost; Fernandes, Ricardo A.
- Cell, Vol. 182, Issue 4
Revisiting Interleukin-12 as a Cancer Immunotherapy Agent
journal, March 2018
- Berraondo, Pedro; Etxeberria, Iñaki; Ponz-Sarvise, Mariano
- Clinical Cancer Research, Vol. 24, Issue 12
Th17 and Regulatory T Cells in Mediating and Restraining Inflammation
journal, March 2010
- Littman, Dan R.; Rudensky, Alexander Y.
- Cell, Vol. 140, Issue 6
Structure and function in rhodopsin: High-level expression of rhodopsin with restricted and homogeneous N-glycosylation by a tetracycline-inducible N-acetylglucosaminyltransferase I-negative HEK293S stable mammalian cell line
journal, October 2002
- Reeves, P. J.; Callewaert, N.; Contreras, R.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 21
Molecular Mechanisms of IFN-γ to Up-Regulate MHC Class I Antigen Processing and Presentation
journal, January 2009
- Zhou, Fang
- International Reviews of Immunology, Vol. 28, Issue 3-4
Interleukin-12 enhances the function and anti-tumor activity in murine and human CD8+ T cells
journal, February 2015
- Rubinstein, Mark P.; Su, Ee Wern; Suriano, Samantha
- Cancer Immunology, Immunotherapy, Vol. 64, Issue 5
T cell receptor antagonist peptides induce positive selection
journal, January 1994
- Hogquist, Kristin A.; Jameson, Stephen C.; Heath, William R.
- Cell, Vol. 76, Issue 1, p. 17-27
Antitumor and antimetastatic activity of interleukin 12 against murine tumors.
journal, October 1993
- Brunda, M. J.; Luistro, L.; Warrier, R. R.
- Journal of Experimental Medicine, Vol. 178, Issue 4
Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12
journal, July 2000
- Yoon, Christina; Johnston, Steven C.; Tang, Jin
- The EMBO Journal, Vol. 19, Issue 14
Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1
journal, January 2018
- Bloch, Yehudi; Bouchareychas, Laura; Merceron, Romain
- Immunity, Vol. 48, Issue 1
Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response
journal, May 2013
- Tseng, D.; Volkmer, J. -P.; Willingham, S. B.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 27
Structural Biology of Shared Cytokine Receptors
journal, April 2009
- Wang, Xinquan; Lupardus, Patrick; LaPorte, Sherry L.
- Annual Review of Immunology, Vol. 27, Issue 1
Isolating and engineering human antibodies using yeast surface display
journal, July 2006
- Chao, Ginger; Lau, Wai L.; Hackel, Benjamin J.
- Nature Protocols, Vol. 1, Issue 2
Collaboration gets the most out of software
journal, September 2013
- Morin, Andrew; Eisenbraun, Ben; Key, Jason
- eLife, Vol. 2
Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes.
journal, September 1989
- Kobayashi, M.; Fitz, L.; Ryan, M.
- Journal of Experimental Medicine, Vol. 170, Issue 3
Cytokine activation induces human memory-like NK cells
journal, December 2012
- Romee, Rizwan; Schneider, Stephanie E.; Leong, Jeffrey W.
- Blood, Vol. 120, Issue 24
Regulation of the Interleukin (IL)-12R β2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells
journal, March 1997
- Szabo, Susanne J.; Dighe, Anand S.; Gubler, Ueli
- Journal of Experimental Medicine, Vol. 185, Issue 5
Therapeutic targeting of the IL-12/23 pathways: generation and characterization of ustekinumab
journal, July 2011
- Benson, Jacqueline M.; Sachs, Clifford W.; Treacy, George
- Nature Biotechnology, Vol. 29, Issue 7
Novel p19 Protein Engages IL-12p40 to Form a Cytokine, IL-23, with Biological Activities Similar as Well as Distinct from IL-12
journal, November 2000
- Oppmann, Birgit; Lesley, Robin; Blom, Bianca
- Immunity, Vol. 13, Issue 5
Structural Basis for the Dual Recognition of IL-12 and IL-23 by Ustekinumab
journal, October 2010
- Luo, Jinquan; Wu, Sheng-Jiun; Lacy, Eilyn R.
- Journal of Molecular Biology, Vol. 402, Issue 5
IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease
journal, September 2017
- Dambuza, Ivy M.; He, Chang; Choi, Jin Kyeong
- Nature Communications, Vol. 8, Issue 1
Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix
journal, October 2019
- Liebschner, Dorothee; Afonine, Pavel V.; Baker, Matthew L.
- Acta Crystallographica Section D Structural Biology, Vol. 75, Issue 10
A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R
journal, June 2002
- Parham, Christi; Chirica, Madaline; Timans, Jacqueline
- The Journal of Immunology, Vol. 168, Issue 11
Direct Interaction of STAT4 with the IL-12 Receptor
journal, August 1999
- Yao, Betty Bei; Niu, Ping; Surowy, Carol S.
- Archives of Biochemistry and Biophysics, Vol. 368, Issue 1
Cooperation of Natural Killer Cell Stimulatory Factor/Interleukin-12 with Other Stimuli in the Induction of Cytokines and Cytotoxic Cell-Associated Molecules in Human T and NK Cells
journal, July 1994
- Aste-Amezaga, Miguel; D'Andrea, Annalisa; Kubin, Marek
- Cellular Immunology, Vol. 156, Issue 2
Structure of an Extracellular gp130 Cytokine Receptor Signaling Complex
journal, March 2001
- Chow, D. -c.
- Science, Vol. 291, Issue 5511
Site-Specific Biotinylation of Purified Proteins Using BirA
book, December 2014
- Fairhead, Michael; Howarth, Mark
- Site-Specific Protein Labeling
Treatment of disseminated ovarian cancer using nonviral interleukin-12 gene therapy delivered intraperitoneally
journal, August 2009
- Fewell, Jason G.; Matar, Majed M.; Rice, Jennifer S.
- The Journal of Gene Medicine, Vol. 11, Issue 8
Neutralization of Human Interleukin 23 by Multivalent Nanobodies Explained by the Structure of Cytokine–Nanobody Complex
journal, August 2017
- Desmyter, Aline; Spinelli, Silvia; Boutton, Carlo
- Frontiers in Immunology, Vol. 8
IL-27, a Heterodimeric Cytokine Composed of EBI3 and p28 Protein, Induces Proliferation of Naive CD4+ T Cells
journal, June 2002
- Pflanz, Stefan; Timans, Jackie C.; Cheung, Jeanne
- Immunity, Vol. 16, Issue 6
CTFFIND4: Fast and accurate defocus estimation from electron micrographs
journal, November 2015
- Rohou, Alexis; Grigorieff, Nikolaus
- Journal of Structural Biology, Vol. 192, Issue 2
A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice: Molecular immunology
journal, April 2016
- Wang, Xiaoqian; Wei, Yinxiang; Xiao, He
- European Journal of Immunology, Vol. 46, Issue 6
An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor
journal, July 2007
- Huyton, T.; Zhang, J. -G.; Luo, C. S.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 31
The JAK-STAT Signaling Pathway: Input and Output Integration
journal, February 2007
- Murray, Peter J.
- The Journal of Immunology, Vol. 178, Issue 5
Intraepithelial Type 1 Innate Lymphoid Cells Are a Unique Subset of IL-12- and IL-15-Responsive IFN-γ-Producing Cells
journal, April 2013
- Fuchs, Anja; Vermi, William; Lee, Jacob S.
- Immunity, Vol. 38, Issue 4
New tools for automated high-resolution cryo-EM structure determination in RELION-3
journal, November 2018
- Zivanov, Jasenko; Nakane, Takanori; Forsberg, Björn O.
- eLife, Vol. 7
IL-12 and IL-7 synergize to control mucosal-associated invariant T-cell cytotoxic responses to bacterial infection
journal, June 2018
- Wallington, Joshua C.; Williams, Anthony P.; Staples, Karl J.
- Journal of Allergy and Clinical Immunology, Vol. 141, Issue 6
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy
journal, February 2017
- Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul
- Nature Methods, Vol. 14, Issue 4
IL-12 p40 monomer is different from other IL-12 family members to selectively inhibit IL-12Rβ1 internalization and suppress EAE
journal, August 2020
- Mondal, Susanta; Kundu, Madhuchhanda; Jana, Malabendu
- Proceedings of the National Academy of Sciences, Vol. 117, Issue 35
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007
- Krissinel, Evgeny; Henrick, Kim
- Journal of Molecular Biology, Vol. 372, Issue 3
Tissue-based map of the human proteome
journal, January 2015
- Uhlen, M.; Fagerberg, L.; Hallstrom, B. M.
- Science, Vol. 347, Issue 6220
IL-21 induces IL-22 production in CD4+ T cells
journal, May 2014
- Yeste, Ada; Mascanfroni, Ivan D.; Nadeau, Meghan
- Nature Communications, Vol. 5, Issue 1
Clinical Trials: IL-12 Deaths: Explanation and a Puzzle
journal, November 1995
- Cohen, J.
- Science, Vol. 270, Issue 5238
Gctf: Real-time CTF determination and correction
journal, January 2016
- Zhang, Kai
- Journal of Structural Biology, Vol. 193, Issue 1
Administration of two macrophage-derived interferon-γ-inducing factors (IL-12 and IL-15) induces a lethal systemic inflammatory response in mice that is dependent on natural killer cells but does not require interferon-γ
journal, March 2002
- Biber, Jennifer L.; Jabbour, Saad; Parihar, Robin
- Cellular Immunology, Vol. 216, Issue 1-2
Anchoring of intratumorally administered cytokines to collagen safely potentiates systemic cancer immunotherapy
journal, June 2019
- Momin, Noor; Mehta, Naveen K.; Bennett, Nitasha R.
- Science Translational Medicine, Vol. 11, Issue 498
IL-2 Modulates the TCR Signaling Threshold for CD8 but Not CD4 T Cell Proliferation on a Single-Cell Level
journal, February 2017
- Au-Yeung, Byron B.; Smith, Geoffrey Alexander; Mueller, James L.
- The Journal of Immunology, Vol. 198, Issue 6
The composition and signaling of the IL-35 receptor are unconventional
journal, February 2012
- Collison, Lauren W.; Delgoffe, Greg M.; Guy, Clifford S.
- Nature Immunology, Vol. 13, Issue 3
The Antibody-Based Delivery of Interleukin-12 to the Tumor Neovasculature Eradicates Murine Models of Cancer in Combination with Paclitaxel
journal, June 2012
- Pasche, Nadine; Wulhfard, Sarah; Pretto, Francesca
- Clinical Cancer Research, Vol. 18, Issue 15
Substantial Energetic Improvement with Minimal Structural Perturbation in a High Affinity Mutant Antibody
journal, October 2004
- Midelfort, K. S.; Hernandez, H. H.; Lippow, S. M.
- Journal of Molecular Biology, Vol. 343, Issue 3
Non-Canonical Interleukin 23 Receptor Complex Assembly
journal, January 2015
- Schröder, Jutta; Moll, Jens M.; Baran, Paul
- Journal of Biological Chemistry, Vol. 290, Issue 1
The Lipid Binding Pleckstrin Homology Domain in UNC-104 Kinesin is Necessary for Synaptic Vesicle Transport in Caenorhabditis elegans
journal, August 2004
- Klopfenstein, Dieter R.; Vale, Ronald D.
- Molecular Biology of the Cell, Vol. 15, Issue 8
The Structure of Interleukin-23 Reveals the Molecular Basis of p40 Subunit Sharing with Interleukin-12
journal, October 2008
- Lupardus, Patrick J.; Garcia, K. Christopher
- Journal of Molecular Biology, Vol. 382, Issue 4
IL-23 Receptor Expression on γδ T Cells Correlates with Their Enhancing or Suppressive Effects on Autoreactive T Cells in Experimental Autoimmune Uveitis
journal, June 2013
- Liang, Dongchun; Zuo, Aijun; Shao, Hui
- The Journal of Immunology, Vol. 191, Issue 3
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Interleukin 23 in the skin: role in psoriasis pathogenesis and selective interleukin 23 blockade as treatment
journal, March 2018
- Chan, Tom C.; Hawkes, Jason E.; Krueger, James G.
- Therapeutic Advances in Chronic Disease, Vol. 9, Issue 5
IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18
journal, April 2020
- Oka, Naoto; Markova, Tzvetanka; Tsuzuki, Kenzo
- Cancer Immunology, Immunotherapy, Vol. 69, Issue 9
Interleukin-12 and the regulation of innate resistance and adaptive immunity
journal, February 2003
- Trinchieri, Giorgio
- Nature Reviews Immunology, Vol. 3, Issue 2
BacMam system for high-level expression of recombinant soluble and membrane glycoproteins for structural studies
journal, December 2008
- Dukkipati, Abhiram; Park, Hyun Ho; Waghray, Deepa
- Protein Expression and Purification, Vol. 62, Issue 2
Intratumoral Delivery of Interleukin 12 Expression Plasmids with In Vivo Electroporation Is Effective for Colon and Renal Cancer
journal, July 2001
- Tamura, Takahiko; Nishi, Toru; Goto, Tomoaki
- Human Gene Therapy, Vol. 12, Issue 10
IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
journal, June 2007
- Zhou, Liang; Ivanov, Ivaylo I.; Spolski, Rosanne
- Nature Immunology, Vol. 8, Issue 9
Fiji: an open-source platform for biological-image analysis
journal, June 2012
- Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin
- Nature Methods, Vol. 9, Issue 7
Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning
journal, May 2012
- Pegram, Hollie J.; Lee, James C.; Hayman, Erik G.
- Blood, Vol. 119, Issue 18
WSX-1 and Glycoprotein 130 Constitute a Signal-Transducing Receptor for IL-27
journal, February 2004
- Pflanz, Stefan; Hibbert, Linda; Mattson, Jeanine
- The Journal of Immunology, Vol. 172, Issue 4
IL-23 Is Critical in the Induction but Not in the Effector Phase of Experimental Autoimmune Encephalomyelitis
journal, February 2007
- Thakker, Paresh; Leach, Michael W.; Kuang, Wen
- The Journal of Immunology, Vol. 178, Issue 4
The inhibitory cytokine IL-35 contributes to regulatory T-cell function
journal, November 2007
- Collison, Lauren W.; Workman, Creg J.; Kuo, Timothy T.
- Nature, Vol. 450, Issue 7169
Hexameric Structure and Assembly of the Interleukin-6/IL-6 -Receptor/gp130 Complex
journal, June 2003
- Boulanger, M. J.
- Science, Vol. 300, Issue 5628
Interleukin 12: still a promising candidate for tumor immunotherapy?
journal, February 2014
- Lasek, Witold; Zagożdżon, Radosław; Jakobisiak, Marek
- Cancer Immunology, Immunotherapy, Vol. 63, Issue 5
IL-23 is essential for T cell–mediated colitis and promotes inflammation via IL-17 and IL-6
journal, May 2006
- Yen, David; Cheung, Jeanne; Scheerens, Heleen
- Journal of Clinical Investigation, Vol. 116, Issue 5
Coadministration of interleukin-18 and interleukin-12 induces a fatal inflammatory response in mice: critical role of natural killer cell interferon-γ production and STAT-mediated signal transduction
journal, August 2000
- Carson, William E.; Dierksheide, Julie E.; Jabbour, Saad
- Blood, Vol. 96, Issue 4
Structural Organization of a Full-Length gp130/LIF-R Cytokine Receptor Transmembrane Complex
journal, September 2008
- Skiniotis, Georgios; Lupardus, Patrick J.; Martick, Monika
- Molecular Cell, Vol. 31, Issue 5
Cytokine therapy reverses NK cell anergy in MHC-deficient tumors
journal, October 2014
- Ardolino, Michele; Azimi, Camillia S.; Iannello, Alexandre
- Journal of Clinical Investigation, Vol. 124, Issue 11
A functional interleukin 12 receptor complex is composed of two -type cytokine receptor subunits
journal, November 1996
- Presky, D. H.; Yang, H.; Minetti, L. J.
- Proceedings of the National Academy of Sciences, Vol. 93, Issue 24
Clinical improvement in psoriasis with specific targeting of interleukin-23
journal, March 2015
- Kopp, Tamara; Riedl, Elisabeth; Bangert, Christine
- Nature, Vol. 521, Issue 7551
Role of Interferon-γ in Mediating the Antitumor Efficacy of Interleukin-12
journal, January 1995
- Brunda, Michael J.; Luistro, Leopoldo; Hendrzak, Jill A.
- Journal of Immunotherapy, Vol. 17, Issue 2
IL-12 Deaths: Explanation and a Puzzle
journal, November 1995
- Cohen, Jon
- Science, Vol. 270, Issue 5238