Small Molecule IL-36γ Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis

Todorović, Viktor; Su, Zhi; Putman, C. Brent; Kakavas, Stevan J.; Salte, Katherine M.; McDonald, Heath A.; Wetter, Joseph B.; Paulsboe, Stephanie E.; Sun, Qi; Gerstein, Clare E.; Medina, Limary; Sielaff, Bernhard; Sadhukhan, Ramkrishna; Stockmann, Henning; Richardson, Paul L.; Qiu, Wei; Argiriadi, Maria A.; Henry, Rodger F.; Herold, J. Martin; Shotwell, J. Brad; McGaraughty, Steve P.; Honore, Prisca; Gopalakrishnan, Sujatha M.; Sun, Chaohong C.; Scott, Victoria E.

doi:10.1038/s41598-019-45626-w

Title: Small Molecule IL-36γ Antagonist as a Novel Therapeutic Approach for Plaque Psoriasis

Journal Article · 24 June 2019 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-019-45626-w · OSTI ID:1577178

^[1]; Su, Zhi ^[1]; Putman, C. Brent ^[1]; Kakavas, Stevan J. ^[1]; Salte, Katherine M. ^[1]; McDonald, Heath A. ^[1]; Wetter, Joseph B. ^[1]; Paulsboe, Stephanie E. ^[1]; Sun, Qi ^[1]; Gerstein, Clare E. ^[1]; Medina, Limary ^[2]; Sielaff, Bernhard ^[2]; Sadhukhan, Ramkrishna ^[2];

^[1];

^[1]; Qiu, Wei ^[1]; Argiriadi, Maria A. ^[2]; Henry, Rodger F. ^[1]; Herold, J. Martin ^[2]; Shotwell, J. Brad ^[1] more »

AbbVie Inc., Chicago, IL (United States)
AbbVie Bioresearch Center, Worcester, MA (United States)

IL-36 cytokines are pro-inflammatory members of the IL-1 family that are upregulated in inflammatory disorders. Specifically, IL-36γ is highly expressed in active psoriatic lesions and can drive pro-inflammatory processes in 3D human skin equivalents supporting a role for this target in skin inflammation. Small molecule antagonists of interleukins have been historically challenging to generate. Nevertheless, we performed a small molecule high-throughput screen to identify IL-36 antagonists using a novel TR-FRET binding assay. Several compounds, including 2-oxypyrimidine containing structural analogs of the marketed endothelin receptor A antagonist Ambrisentan, were identified as hits from the screen. A-552 was identified as a the most potent antagonist of human IL-36γ, but not the closely related family member IL-36α, was capable of attenuating IL-36γ induced responses in mouse and human disease models. Additionally, x-ray crystallography studies identified key amino acid residues in the binding pocket present in human IL-36γ that are absent in human IL-36α. A-552 represents a first-in-class small molecule antagonist of IL-36 signaling that could be used as a chemical tool to further investigate the role of this pathway in inflammatory skin diseases such as psoriasis.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1577178

Journal Information:: Scientific Reports, Vol. 9, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (76)

Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation Blumberg, Hal; Dinh, Huyen; Trueblood, Esther S. The Journal of Experimental Medicine, Vol. 204, Issue 11 https://doi.org/10.1084/jem.20070157	journal	October 2007
Interleukin-36 (IL-36) Ligands Require Processing for Full Agonist (IL-36α, IL-36β, and IL-36γ) or Antagonist (IL-36Ra) Activity Towne, Jennifer E.; Renshaw, Blair R.; Douangpanya, Jason Journal of Biological Chemistry, Vol. 286, Issue 49 https://doi.org/10.1074/jbc.M111.267922	journal	September 2011
A hierarchical approach to all-atom protein loop prediction Jacobson, Matthew P.; Pincus, David L.; Rapp, Chaya S. Proteins: Structure, Function, and Bioinformatics, Vol. 55, Issue 2 https://doi.org/10.1002/prot.10613	journal	March 2004
Structural insights into the interaction of IL-33 with its receptors Liu, X.; Hammel, M.; He, Y. Proceedings of the National Academy of Sciences, Vol. 110, Issue 37 https://doi.org/10.1073/pnas.1308651110	journal	August 2013
Distinct expression of interleukin (IL)-36 α, β and γ , their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease : IL-36 cytokines in inflammatory diseases Boutet, M. -A.; Bart, G.; Penhoat, M. Clinical & Experimental Immunology, Vol. 184, Issue 2 https://doi.org/10.1111/cei.12761	journal	February 2016
IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions D'Erme, Angelo Massimiliano; Wilsmann-Theis, Dagmar; Wagenpfeil, Julia Journal of Investigative Dermatology, Vol. 135, Issue 4 https://doi.org/10.1038/jid.2014.532	journal	April 2015
Binding of small molecules to an adaptive protein-protein interface Arkin, M. R.; Randal, M.; DeLano, W. L. Proceedings of the National Academy of Sciences, Vol. 100, Issue 4 https://doi.org/10.1073/pnas.252756299	journal	February 2003
An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target Mahil, Satveer K.; Catapano, Marika; Di Meglio, Paola Science Translational Medicine, Vol. 9, Issue 411 https://doi.org/10.1126/scitranslmed.aan2514	journal	October 2017
Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation Sullivan, Graeme P.; Davidovich, Pavel B.; Sura-Trueba, Sylvia FEBS Open Bio, Vol. 8, Issue 5 https://doi.org/10.1002/2211-5463.12406	journal	March 2018
The Interleukin-23/Interleukin-17 Axis Links Adaptive and Innate Immunity in Psoriasis Schön, Michael P.; Erpenbeck, Luise Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.01323	journal	June 2018
Small-molecule control of cytokine function: new opportunities for treating immune disorders Sundberg, Thomas B.; Xavier, Ramnik J.; Schreiber, Stuart L. Current Opinion in Chemical Biology, Vol. 23 https://doi.org/10.1016/j.cbpa.2014.08.013	journal	December 2014
Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines Henry, Conor M.; Sullivan, Graeme P.; Clancy, Danielle M. Cell Reports, Vol. 14, Issue 4 https://doi.org/10.1016/j.celrep.2015.12.072	journal	February 2016
Old and New Biological Therapies for Psoriasis Rønholt, Kirsten; Iversen, Lars International Journal of Molecular Sciences, Vol. 18, Issue 11 https://doi.org/10.3390/ijms18112297	journal	November 2017
IL-36 receptor antagonistic antibodies inhibit inflammatory responses in preclinical models of psoriasiform dermatitis Su, Zhi; Paulsboe, Stephanie; Wetter, Joseph Experimental Dermatology, Vol. 28, Issue 2 https://doi.org/10.1111/exd.13841	journal	December 2018
The structural basis for receptor recognition of human interleukin-18 Tsutsumi, Naotaka; Kimura, Takeshi; Arita, Kyohei Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms6340	journal	December 2014
Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions Gabay, Cem; Towne, Jennifer E. Journal of Leukocyte Biology, Vol. 97, Issue 4 https://doi.org/10.1189/jlb.3RI1014-495R	journal	February 2015
Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies Ganesan, Rajkumar; Raymond, Ernest L.; Mennerich, Detlev mAbs, Vol. 9, Issue 7 https://doi.org/10.1080/19420862.2017.1353853	journal	July 2017
Cell-Surface Receptor–Ligand Interaction Analysis with Homogeneous Time-Resolved FRET and Metabolic Glycan Engineering: Application to Transmembrane and GPI-Anchored Receptors Stockmann, Henning; Todorovic, Viktor; Richardson, Paul L. Journal of the American Chemical Society, Vol. 139, Issue 46 https://doi.org/10.1021/jacs.7b09359	journal	November 2017
High-Resolution Structure of Murine Interleukin 1 Homologue IL-1F5 Reveals Unique Loop Conformations for Receptor Binding Specificity ^† ^, ^‡ Dunn, Eleanor F.; Gay, Nicholas J.; Bristow, Adrian F. Biochemistry, Vol. 42, Issue 37 https://doi.org/10.1021/bi0341197	journal	September 2003
Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery Lo, Mei-Chu; Aulabaugh, Ann; Jin, Guixian Analytical Biochemistry, Vol. 332, Issue 1 https://doi.org/10.1016/j.ab.2004.04.031	journal	September 2004
Mechanistic and pharmacological assessment of murine IL-23 mediated psoriasiform dermatitis; implications for drug discovery Gauld, Stephen B.; Gauvin, Donna; Olson, Lauren Journal of Dermatological Science, Vol. 92, Issue 1 https://doi.org/10.1016/j.jdermsci.2018.08.001	journal	October 2018
Psoriasis pathogenesis and the development of novel targeted immune therapies Hawkes, Jason E.; Chan, Tom C.; Krueger, James G. Journal of Allergy and Clinical Immunology, Vol. 140, Issue 3 https://doi.org/10.1016/j.jaci.2017.07.004	journal	September 2017
The use of skin models in drug development Mathes, Stephanie H.; Ruffner, Heinz; Graf-Hausner, Ursula Advanced Drug Delivery Reviews, Vol. 69-70 https://doi.org/10.1016/j.addr.2013.12.006	journal	April 2014
Neutrophil elastase targets virulence factors of enterobacteria Weinrauch, Yvette; Drujan, Doreen; Shapiro, Steven D. Nature, Vol. 417, Issue 6884 https://doi.org/10.1038/417091a	journal	May 2002
Suppression of Molecular Inflammatory Pathways by Toll-Like Receptor 7, 8, and 9 Antagonists in a Model of IL-23-Induced Skin Inflammation Suárez-Fariñas, Mayte; Arbeit, Robert; Jiang, Weiwen PLoS ONE, Vol. 8, Issue 12 https://doi.org/10.1371/journal.pone.0084634	journal	December 2013
Structural insights into the assembly and activation of IL-1β with its receptors Wang, Dongli; Zhang, Senyan; Li, Liang Nature Immunology, Vol. 11, Issue 10 https://doi.org/10.1038/ni.1925	journal	August 2010
Structure of the activating IL-1 receptor signaling complex Thomas, Christoph; Bazan, J. Fernando; Garcia, K. Christopher Nature Structural & Molecular Biology, Vol. 19, Issue 4 https://doi.org/10.1038/nsmb.2260	journal	March 2012
Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36γ Ainscough, Joseph S.; Macleod, Tom; McGonagle, Dennis Proceedings of the National Academy of Sciences, Vol. 114, Issue 13 https://doi.org/10.1073/pnas.1620954114	journal	March 2017
Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality Arkin, Michelle R.; Tang, Yinyan; Wells, James A. Chemistry & Biology, Vol. 21, Issue 9 https://doi.org/10.1016/j.chembiol.2014.09.001	journal	September 2014
IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis Johnston, Andrew; Xing, Xianying; Wolterink, Liza Journal of Allergy and Clinical Immunology, Vol. 140, Issue 1 https://doi.org/10.1016/j.jaci.2016.08.056	journal	July 2017
Development of a Novel Noncompetitive Antagonist of IL-1 Receptor Quiniou, Christiane; Sapieha, Przemyslaw; Lahaie, Isabelle The Journal of Immunology, Vol. 180, Issue 10 https://doi.org/10.4049/jimmunol.180.10.6977	journal	May 2008
Degradation of Outer Membrane Protein A in Escherichia coli Killing by Neutrophil Elastase Belaaouaj, A. a. Science, Vol. 289, Issue 5482 https://doi.org/10.1126/science.289.5482.1185	journal	August 2000
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Identification of Potential Small Molecule Allosteric Modulator Sites on IL-1R1 Ectodomain Using Accelerated Conformational Sampling Method Yang, Chao-Yie PLOS ONE, Vol. 10, Issue 2 https://doi.org/10.1371/journal.pone.0118671	journal	February 2015
Identification, cloning and characterisation of interleukin-1F5 (IL-36RN) in the chicken Gibson, M. S.; Salmon, N.; Bird, S. Developmental & Comparative Immunology, Vol. 38, Issue 1 https://doi.org/10.1016/j.dci.2012.04.014	journal	September 2012
Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist Klementiev, Boris; Li, Shizhong; Korshunova, Irina Journal of Neuroinflammation, Vol. 11, Issue 1 https://doi.org/10.1186/1742-2094-11-27	journal	January 2014
Apremilast for the management of moderate to severe plaque psoriasis Vangipuram, Ramya; Alikhan, Ali Expert Review of Clinical Pharmacology, Vol. 10, Issue 4 https://doi.org/10.1080/17512433.2017.1293519	journal	February 2017
IL-36 Promotes Myeloid Cell Infiltration, Activation, and Inflammatory Activity in Skin Foster, Alexander M.; Baliwag, Jaymie; Chen, Cynthia S. The Journal of Immunology, Vol. 192, Issue 12 https://doi.org/10.4049/jimmunol.1301481	journal	May 2014
The Interleukin-1 Family: Back to the Future Garlanda, Cecilia; Dinarello, Charles A.; Mantovani, Alberto Immunity, Vol. 39, Issue 6 https://doi.org/10.1016/j.immuni.2013.11.010	journal	December 2013
Time-Resolved Fluorescence Resonance Energy Transfer [TR-FRET] Assays for Biochemical Processes Ergin, Ekin; Dogan, Arin; Parmaksiz, Mahmut Current Pharmaceutical Biotechnology, Vol. 17, Issue 14 https://doi.org/10.2174/1389201017666160809164527	journal	November 2016
Molecular Determinants of Agonist and Antagonist Signaling through the IL-36 Receptor Günther, Sebastian; Sundberg, Eric J. The Journal of Immunology, Vol. 193, Issue 2 https://doi.org/10.4049/jimmunol.1400538	journal	June 2014
IL-1RL2 and Its Ligands Contribute to the Cytokine Network in Psoriasis Blumberg, Hal; Dinh, Huyen; Dean, Charles The Journal of Immunology, Vol. 185, Issue 7 https://doi.org/10.4049/jimmunol.1000313	journal	September 2010
Data processing and analysis with the autoPROC toolbox Vonrhein, Clemens; Flensburg, Claus; Keller, Peter Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444911007773	journal	March 2011
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
The psoriasis-associated IL-17A induces and cooperates with IL-36 cytokines to control keratinocyte differentiation and function Pfaff, Carolina M.; Marquardt, Yvonne; Fietkau, Katharina Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-15892-7	journal	November 2017
Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation Sullivan, Graeme P.; Davidovich, Pavel B.; Sura-Trueba, Sylvia FEBS Open Bio, Vol. 8, Issue 5 https://doi.org/10.1002/2211-5463.12406	journal	March 2018
Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery Lo, Mei-Chu; Aulabaugh, Ann; Jin, Guixian Analytical Biochemistry, Vol. 332, Issue 1 https://doi.org/10.1016/j.ab.2004.04.031	journal	September 2004
The use of skin models in drug development Mathes, Stephanie H.; Ruffner, Heinz; Graf-Hausner, Ursula Advanced Drug Delivery Reviews, Vol. 69-70 https://doi.org/10.1016/j.addr.2013.12.006	journal	April 2014
Small-molecule control of cytokine function: new opportunities for treating immune disorders Sundberg, Thomas B.; Xavier, Ramnik J.; Schreiber, Stuart L. Current Opinion in Chemical Biology, Vol. 23 https://doi.org/10.1016/j.cbpa.2014.08.013	journal	December 2014
Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines Henry, Conor M.; Sullivan, Graeme P.; Clancy, Danielle M. Cell Reports, Vol. 14, Issue 4 https://doi.org/10.1016/j.celrep.2015.12.072	journal	February 2016
Identification, cloning and characterisation of interleukin-1F5 (IL-36RN) in the chicken Gibson, M. S.; Salmon, N.; Bird, S. Developmental & Comparative Immunology, Vol. 38, Issue 1 https://doi.org/10.1016/j.dci.2012.04.014	journal	September 2012
The Interleukin-1 Family: Back to the Future Garlanda, Cecilia; Dinarello, Charles A.; Mantovani, Alberto Immunity, Vol. 39, Issue 6 https://doi.org/10.1016/j.immuni.2013.11.010	journal	December 2013
IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis Johnston, Andrew; Xing, Xianying; Wolterink, Liza Journal of Allergy and Clinical Immunology, Vol. 140, Issue 1 https://doi.org/10.1016/j.jaci.2016.08.056	journal	July 2017
Psoriasis Boehncke, Wolf-Henning; Schön, Michael P. The Lancet, Vol. 386, Issue 9997 https://doi.org/10.1016/s0140-6736(14)61909-7	journal	September 2015
Cell-Surface Receptor–Ligand Interaction Analysis with Homogeneous Time-Resolved FRET and Metabolic Glycan Engineering: Application to Transmembrane and GPI-Anchored Receptors Stockmann, Henning; Todorovic, Viktor; Richardson, Paul L. Journal of the American Chemical Society, Vol. 139, Issue 46 https://doi.org/10.1021/jacs.7b09359	journal	November 2017
IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions D'Erme, Angelo Massimiliano; Wilsmann-Theis, Dagmar; Wagenpfeil, Julia Journal of Investigative Dermatology, Vol. 135, Issue 4 https://doi.org/10.1038/jid.2014.532	journal	April 2015
The structural basis for receptor recognition of human interleukin-18 Tsutsumi, Naotaka; Kimura, Takeshi; Arita, Kyohei Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms6340	journal	December 2014
Structure of the activating IL-1 receptor signaling complex Thomas, Christoph; Bazan, J. Fernando; Garcia, K. Christopher Nature Structural & Molecular Biology, Vol. 19, Issue 4 https://doi.org/10.1038/nsmb.2260	journal	March 2012
Structural insights into the interaction of IL-33 with its receptors Liu, X.; Hammel, M.; He, Y. Proceedings of the National Academy of Sciences, Vol. 110, Issue 37 https://doi.org/10.1073/pnas.1308651110	journal	August 2013
Binding of small molecules to an adaptive protein-protein interface Arkin, M. R.; Randal, M.; DeLano, W. L. Proceedings of the National Academy of Sciences, Vol. 100, Issue 4 https://doi.org/10.1073/pnas.252756299	journal	February 2003
Structural and Functional Attributes of the Interleukin-36 Receptor Yi, Guanghui; Ybe, Joel A.; Saha, Siddhartha S. Journal of Biological Chemistry, Vol. 291, Issue 32 https://doi.org/10.1074/jbc.m116.723064	journal	June 2016
Quantitative ligand and receptor binding studies reveal the mechanism of interleukin-36 (IL-36) pathway activation Zhou, Li; Todorovic, Viktor; Kakavas, Steve Journal of Biological Chemistry, Vol. 293, Issue 2 https://doi.org/10.1074/jbc.m117.805739	journal	November 2017
Interleukin (IL)-1F6, IL-1F8, and IL-1F9 Signal through IL-1Rrp2 and IL-1RAcP to Activate the Pathway Leading to NF-κB and MAPKs Towne, Jennifer E.; Garka, Kirsten E.; Renshaw, Blair R. Journal of Biological Chemistry, Vol. 279, Issue 14 https://doi.org/10.1074/jbc.m400117200	journal	January 2004
Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies Ganesan, Rajkumar; Raymond, Ernest L.; Mennerich, Detlev mAbs, Vol. 9, Issue 7 https://doi.org/10.1080/19420862.2017.1353853	journal	July 2017
Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation Blumberg, Hal; Dinh, Huyen; Trueblood, Esther S. The Journal of Experimental Medicine, Vol. 204, Issue 11 https://doi.org/10.1084/jem.20070157	journal	October 2007
Distinct expression of interleukin (IL)-36 α, β and γ , their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease : IL-36 cytokines in inflammatory diseases Boutet, M. -A.; Bart, G.; Penhoat, M. Clinical & Experimental Immunology, Vol. 184, Issue 2 https://doi.org/10.1111/cei.12761	journal	February 2016
IL-36 receptor antagonistic antibodies inhibit inflammatory responses in preclinical models of psoriasiform dermatitis Su, Zhi; Paulsboe, Stephanie; Wetter, Joseph Experimental Dermatology, Vol. 28, Issue 2 https://doi.org/10.1111/exd.13841	journal	December 2018
Degradation of Outer Membrane Protein A in Escherichia coli Killing by Neutrophil Elastase Belaaouaj, A. a. Science, Vol. 289, Issue 5482 https://doi.org/10.1126/science.289.5482.1185	journal	August 2000
Psoriasiform dermatitis is driven by IL-36–mediated DC-keratinocyte crosstalk Tortola, Luigi; Rosenwald, Esther; Abel, Brian Journal of Clinical Investigation, Vol. 122, Issue 11 https://doi.org/10.1172/jci63451	journal	October 2012
Suppression of Molecular Inflammatory Pathways by Toll-Like Receptor 7, 8, and 9 Antagonists in a Model of IL-23-Induced Skin Inflammation Suárez-Fariñas, Mayte; Arbeit, Robert; Jiang, Weiwen PLoS ONE, Vol. 8, Issue 12 https://doi.org/10.1371/journal.pone.0084634	journal	December 2013
Identification of Potential Small Molecule Allosteric Modulator Sites on IL-1R1 Ectodomain Using Accelerated Conformational Sampling Method Yang, Chao-Yie PLOS ONE, Vol. 10, Issue 2 https://doi.org/10.1371/journal.pone.0118671	journal	February 2015
The psoriasis-associated IL-17A induces and cooperates with IL-36 cytokines to control keratinocyte differentiation and function Pfaff, Carolina M.; Marquardt, Yvonne; Fietkau, Katharina RWTH Aachen University https://doi.org/10.18154/rwth-conv-222234	text	January 2017
Time-Resolved Fluorescence Resonance Energy Transfer [TR-FRET] Assays for Biochemical Processes Ergin, Ekin; Dogan, Arin; Parmaksiz, Mahmut Current Pharmaceutical Biotechnology, Vol. 17, Issue 14 https://doi.org/10.2174/1389201017666160809164527	journal	November 2016
Old and New Biological Therapies for Psoriasis Rønholt, Kirsten; Iversen, Lars International Journal of Molecular Sciences, Vol. 18, Issue 11 https://doi.org/10.3390/ijms18112297	journal	November 2017
IL-36 Promotes Myeloid Cell Infiltration, Activation, and Inflammatory Activity in Skin Foster, Alexander M.; Baliwag, Jaymie; Chen, Cynthia S. The Journal of Immunology, Vol. 192, Issue 12 https://doi.org/10.4049/jimmunol.1301481	journal	May 2014
Molecular Determinants of Agonist and Antagonist Signaling through the IL-36 Receptor Günther, Sebastian; Sundberg, Eric J. The Journal of Immunology, Vol. 193, Issue 2 https://doi.org/10.4049/jimmunol.1400538	journal	June 2014