Article
Medicine, Research & Experimental
Aeri Park, Tae-Hwe Heo
Summary: IL-17A is a crucial pro-inflammatory cytokine in autoimmune diseases, which can be inhibited by fenofibrate, a small molecule drug. Fenofibrate regulates autophagy and exerts anti-inflammatory effects, suggesting its potential as a therapeutic for psoriasis and other autoimmune diseases.
Article
Immunology
Saeideh Sadat Shobeiri, MohammadAli Rezaee, Safoora Pordel, Navideh Haghnnavaz, Mohammadreza Dashti, Malihe Moghadam, Mojtaba Sankian
Summary: The therapeutic effects of M2 and M7 anti-IL17A ssDNA aptamers were evaluated in an IMQ-induced psoriasis mouse model. The application of aptamers significantly improved psoriatic lesions and decreased the expression levels of inflammatory factors.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Immunology
Wenjuan Yang, Rukun He, Hao Qu, Wenwen Lian, Yue Xue, Tao Wang, Wenlong Lin, Peishuo Zhu, Meng Xia, Lihua Lai, Qingqing Wang
Summary: FXYD3 is upregulated in the lesional skin of psoriasis patients and mice with IMQ-induced psoriasis. It promotes IL-17A signaling in keratinocytes, leading to inflammation and the expression of proinflammatory factors, exacerbating psoriasis. Targeting FXYD3 could be a potential therapeutic approach for psoriasis.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Hung-Lin Chen, Chia-Hui Lo, Chi-Chun Huang, Meng-Ping Lu, Po-Yuan Hu, Chang-Shan Chen, Di-Yen Chueh, Peilin Chen, Teng-Nan Lin, Yuan-Hsin Lo, Yu-Ping Hsiao, Daniel K. Hsu, Fu-Tong Liu
Summary: The study found that the expression of galectin-7 is reduced in skin lesions of psoriasis patients, and IL-17A and TNF-alpha suppress galectin-7 expression in human keratinocytes. Galectin-7 attenuates the production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway when cells are stimulated with IL-17A. Fluvastatin was identified as an inducer of galectin-7 expression and showed potential in reducing IL-6 and IL-8 production induced by IL-17A.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Immunology
Qiang Dong, Dan Li, Bi Bo Xie, Li Hua Hu, Jia Huang, Xiao Xiao Jia, Yan Li Tang, Gan Hong Liu, Ning Ning Shen, Xiao Bing Yu
Summary: Treatment of psoriasis with Adalimumab and secukinumab can induce changes in multiple proteins in the lesions, overlapping effects on immune response and processes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xinran Xie, Lei Zhang, Yan Lin, Xin Liu, Ning Wang, Ping Li
Summary: In this study, a mouse model of psoriasiform dermatitis was established by intradermal IL-17A injection in STAT3 overexpressing mice. Transcriptome analyses showed that IL-17A exacerbated the pathological features of skin lesions in STAT3 overexpressing mice, which were highly consistent with those observed in psoriasis patients. Functional enrichment analysis revealed that the core differentially expressed genes were closely related to immune response, chemotaxis, and cornified envelope. The major KEGG enrichment pathways included IL-17 and Toll-like receptor signaling pathways.
Article
Multidisciplinary Sciences
Anissa Fries, Fanny Saidoune, Francois Kuonen, Isabelle Dupanloup, Nadine Fournier, Ana Cristina Guerra de Souza, Muzlifah Haniffa, Feiyang Ma, Johann E. Gudjonsson, Lennart Roesner, Yang Li, Thomas Werfel, Curdin Conrad, Raphael Gottardo, Robert L. Modlin, Jeremy Di Domizio, Michel Gilliet
Summary: This study establishes the role of interleukin 26 (IL-26) in the generation of IL-17A producing Th17 CD4(+) T cells, indicating its involvement in the pathogenic response of psoriasis. IL-26-producing cells infiltrate psoriatic skin and promote their own differentiation into IL17A-producing T(H)17 cells through epithelial crosstalk involving paracrine production of TGF-& beta;1.
NATURE COMMUNICATIONS
(2023)
Article
Rheumatology
Anella Saviano, Adel Abo Manosour, Federica Raucci, Francesco Merlino, Noemi Marigliano, Anna Schettino, Mussarat Wahid, Jenefa Begum, Andrew Filer, Julia E. Manning, Gian Marco Casillo, Marialuisa Piccolo, Maria Grazia Ferraro, Simona Marzano, Pasquale Russomanno, Rosa Bellavita, Carlo Irace, Jussara Amato, Mohammed Alfaifi, Peter Rimmer, Tariq Iqbal, Stefano Pieretti, Valentina Vellecco, Francesco Caso, Luisa Costa, Roberto Giacomelli, Raffaele Scarpa, Giuseppe Cirino, Mariarosaria Bucci, Helen M. McGettrick, Paolo Grieco, Asif Jilani Iqbal, Francesco Maione
Summary: This study identified a novel IL-17A/F-derived peptide and generated a new anti-IL-17 antibody that can effectively reverse the pro-inflammatory actions of IL-17A/F. The antibody showed less off-target effects compared to the current gold-standard biologic. Preclinical and clinical evidence demonstrated the high efficacy and therapeutic potency of the antibody in patients with IMIDs.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Xiuju Dai, Masamoto Murakami, Ken Shiraishi, Jun Muto, Mikiko Tohyama, Hideki Mori, Ryo Utsunomiya, Koji Sayama
Summary: This study reveals a potential mechanism by which EGFR signaling contributes to the pathogenesis of psoriasis. Different EGFR ligands stimulate the production of psoriasis signature genes in epidermal cells, thereby enhancing the effects of IL-17A signaling.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Bennet Frost, Maria Schmidt, Benjamin Klein, Henry Loeffler-Wirth, Knuth Krohn, Timo Reidenbach, Hans Binder, Antonia Stubenvoll, Jan C. Simon, Anja Saalbach, Manfred Kunz
Summary: This study used single-cell transcriptomic analyses to identify immune cell and nonimmune cell populations involved in psoriasis. Different immune-activated cell types and abnormal expression of IL-14, IL-18, and IL-32 were found in psoriatic skin. These findings provide insights into the role of IL-14, IL-18, and IL-32 in psoriasis pathogenesis.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Michael Levraut, Veronique Bourg, Nicolas Capet, Adrien Delourme, Jerome Honnorat, Pierre Thomas, Christine Lebrun-Frenay
Summary: In non-NMDAR AE patients, the concentration of CSF IL-17A is elevated, correlated with disease severity and ICU admission, but not associated with the 1-year clinical outcome.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Chun-Wen Chan, Hung-Wen Chen, Yu-Wen Wang, Chia- Lin, Ya-Hui Chuang
Summary: This study found that the Th17 cell-derived cytokine IL-21 plays a role in the pathogenesis of PBC, exacerbating liver inflammation and fibrosis and increasing the numbers and effector activities of CD8+ T cells.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Immunology
Tithi Roy, Sergette Banang-Mbeumi, Samuel T. Boateng, Emmanuelle M. Ruiz, Roxane-Cherille N. Chamcheu, Lin Kang, Judy A. King, Anthony L. Walker, Bolni Marius Nagalo, Konstantin G. Kousoulas, Stephane Esnault, Shile Huang, Jean Christopher Chamcheu
Summary: Fisetin has potential therapeutic effects on refractory psoriasis by inhibiting abnormal immune response, promoting keratinocyte differentiation and autophagy, and reducing disease inflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Dermatology
Burak Aksan, Aysegul Basak Akadam-Teker
Summary: The TT genotype and T allele of IL-17A rs10484879 are associated with an increased risk of psoriasis in the Turkish population. This study suggests that IL-17A polymorphism may play a role in the pathogenesis of the disease. The IL-17A serum levels were also found to be associated with the genotype distribution.
ARCHIVES OF DERMATOLOGICAL RESEARCH
(2022)
Article
Immunology
Matheus Braga, Fernanda Formaggi Lara-Armi, Janisleya Silva Ferreira Neves, Marco Antonio Rocha-Loures, Mariana de Souza Terron-Monich, Larissa Danielle Bahls-Pinto, Quirino Alves de Lima Neto, Joana Maira Valentini Zacarias, Ana Maria Sell, Jeane Eliete Laguila Visentainer
Summary: The IL10 -1082 A>G (rs1800896) genotype is associated with AS, with AS patients having higher levels of IL-10 in serum, and the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Shuai Shao, Lam C. Tsoi, Mrinal K. Sarkar, Xianying Xing, Ke Xue, Ranjitha Uppala, Celine C. Berthier, Chang Zeng, Matthew Patrick, Allison C. Billi, Joseph Fullmer, Maria A. Beamer, Bethany Perez-White, Spiro Getsios, Andrew Schuler, John J. Voorhees, Sung Choi, Paul Harms, J. Michelle Kahlenberg, Johann E. Gudjonsson
SCIENCE TRANSLATIONAL MEDICINE
(2019)
Article
Allergy
Lam C. Tsoi, Elke Rodriguez, Dora Stoelzl, Ulrike Wehkamp, Jingru Sun, Sascha Gerdes, Mrinal K. Sarkar, Matthias Huebenthal, Chang Zeng, Ranjitha Uppala, Xianying Xing, Frederieke Thielking, Allison C. Billi, William R. Swindell, Alanna Shefler, Jiahan Chen, Matthew T. Patrick, Paul W. Harms, J. Michelle Kahlenberg, Bethany E. Perez White, Emanual Maverakis, Johann E. Gudjonsson, Stephan Weidinger
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2020)
Editorial Material
Medicine, Research & Experimental
Allison C. Billi, Mrinal K. Sarkar, Johann E. Gudjonsson
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Dermatology
Sirisha Sirobhushanam, Navya Parsa, Tamra J. Reed, Celine C. Berthier, Mrinal K. Sarkar, Grace A. Hile, Lam C. Tsoi, Josh Banfield, Craig Dobry, Alexander R. Horswill, Johann E. Gudjonsson, J. Michelle Kahlenberg
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2020)
Article
Medicine, Research & Experimental
Allison C. Billi, Jessica E. Ludwig, Yi Fritz, Richard Rozic, William R. Swindell, Lam C. Tsoi, Dennis Gruzska, Shahla Abdollahi-Roodsaz, Xianying Xing, Doina Diaconu, Ranjitha Uppala, Maya Camhi, Philip A. Klenotic, Mrinal K. Sarkar, M. Elaine Husni, Jose U. Scher, Christine McDonald, J. Michelle Kahlenberg, Ronald J. Midura, Johann E. Gudjonsson, Nicole L. Ward
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
Jeffery T. Kwock, Chelsea Handfield, Jutamas Suwanpradid, Peter Hoang, Michael J. McFadden, Kevin F. Labagnara, Lauren Floyd, Jessica Shannon, Ranjitha Uppala, Mrinal K. Sarkar, Johann E. Gudjonsson, David L. Corcoran, Helen M. Lazear, Gregory Sempowski, Stacy M. Horner, Amanda S. MacLeod
Article
Cell Biology
Cory L. Simpson, Mariko K. Tokito, Ranjitha Uppala, Mrinal K. Sarkar, Johann E. Gudjonsson, Erika L. F. Holzbaur
Summary: This study reveals that regulated breakdown of mitochondria is critical for epidermal development, with keratinocytes in the upper layers initiating mitochondrial fragmentation, depolarization, and acidification. The mitophagy receptor NIX and DRP1 play essential roles in driving epidermal morphogenesis by promoting mitochondrial degradation in the terminal differentiation of keratinocytes.
Article
Dermatology
Shuai Shao, Lam C. Tsoi, William R. Swindell, Jiaoling Chen, Ranjitha Uppala, Allison C. Billi, Xianying Xing, Chang Zeng, Mrinal K. Sarkar, Rachael Wasikowski, Yanyun Jiang, Joseph Kirma, Jingru Sun, Olesya Plazyo, Gang Wang, Paul W. Harms, John J. Voorhees, Nicole L. Ward, Feiyang Ma, Matteo Pellegrini, Alexander Merleev, Bethany E. Perez White, Robert L. Modlin, Bogi Andersen, Emanual Maverakis, Stephan Weidinger, J. Michelle Kahlenberg, Johann E. Gudjonsson
Summary: The research reveals the critical role of IRAK2 in the severity of atopic dermatitis and psoriasis, with inhibition of IRAK2 normalizing differentiation and inflammation. These findings suggest that IRAK2 promotes feed-forward amplification of inflammatory responses in the skin through modulation of differentiation pathways and inflammatory responses.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Allergy
Lam C. Tsoi, Matthew T. Patrick, Shao Shuai, Mrinal K. Sarkar, Sunyi Chi, Bethany Ruffino, Allison C. Billi, Xianying Xing, Ranjitha Uppala, Cheng Zang, Joseph Fullmer, Zhi He, Emanual Maverakis, Nehal N. Mehta, Bethany E. Perez White, Spiro Getsios, Yolanda Helfrich, John J. Voorhees, J. Michelle Kahlenberg, Stephan Weidinger, Johann E. Gudjonsson
Summary: This study evaluates the use of baseline molecular expression profiling to assess treatment outcome for patients with psoriasis. The results show a correlation between clinical response and molecular changes, particularly for genes responding to IL-17A/TNF in keratinocytes. Baseline gene expressions in nonlesional skin were found to be the best marker of treatment response, and cytokine gene signatures enriched in baseline nonlesional skin had strong correlations with treatment improvement.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Shuai Shao, Jiaoling Chen, William R. Swindell, Lam C. Tsoi, Xianying Xing, Feiyang Ma, Ranjitha Uppala, Mrinal K. Sarkar, Olesya Plazyo, Allison C. Billi, Rachael Wasikowski, Kathleen M. Smith, Prisca Honore, Victoria E. Scott, Emanual Maverakis, J. Michelle Kahlenberg, Gang Wang, Nicole L. Ward, Paul W. Harms, Johann E. Gudjonsson
Summary: Through global transcriptomic profiling, it was found that there is a high overlap between plaque psoriasis and pityriasis rubra pilaris skin lesions, indicating a common molecular signature between these skin disorders. The study highlights the important role of phospholipases as regulators of epidermal barrier homeostasis and inflammation, identifying them as a shared pathogenic mechanism between PRP and psoriasis, and as potential therapeutic targets for both diseases.
Article
Dermatology
Lam C. Tsoi, Xianying Xing, Enze Xing, Rachael Wasikowski, Shuai Shao, Chang Zeng, Olesya Plazyo, Joseph Kirma, Yanyung Jiang, Allison C. Billi, Mrinal K. Sarkar, Jessica L. Turnier, Ranjitha Uppala, Kathleen M. Smith, Yolanda Helfrich, John J. Voorhees, Emanual Maverakis, Robert L. Modlin, J. Michelle Kahlenberg, Victoria E. Scott, Johann E. Gudjonsson
Summary: This study demonstrates that tape stripping with optimized high-resolution transcriptomic profiling can effectively assess and characterize inflammatory responses in the skin. By comparing different samples and sampling methods, the study shows that tape stripping can capture the transcriptome of the upper layers of the skin, providing insights into the molecular components of the immune amplification pathway in psoriasis. Additionally, the study suggests that nonlesional psoriatic skin exhibits activated, proinflammatory changes, which are not captured by full-thickness skin biopsy transcriptome profiling.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Genetics & Heredity
Alanna Shefler, Matthew T. Patrick, Rachael Wasikowski, Jiahan Chen, Mrinal K. Sarkar, Johann E. Gudjonsson, Lam C. Tsoi
Summary: This review characterizes prominent skin-expressing lncRNAs using large scale genomic data, providing insights into their potential roles in the pathology of inflammatory skin diseases like atopic dermatitis and psoriasis. The review also highlights the cell type specificity of lncRNAs and their potential as mediators in cytokine-stimulated pathways.
FRONTIERS IN GENETICS
(2022)
Article
Cell Biology
Arnaud Goepfert, Carmen Barske, Sylvie Lehmann, Emmanuelle Wirth, Joschka Willemsen, Johann E. Gudjonsson, Nicole L. Ward, Mrinal K. Sarkar, Rene Hemmig, Frank Kolbinger, Jean-Michel Rondeau
Summary: Through crystallography, biophysics, and mutational studies, this research demonstrates that IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization, leading to the formation of a 2:2:2 hexameric signaling assembly. The formation of the IL-17 signalosome potentiates IL-17-induced IL-36 gamma and CXCL1 mRNA expression in human keratinocytes compared to a dimerization-defective IL-17RA variant.
Article
Multidisciplinary Sciences
Jeffrey Y. Zhou, Mrinal K. Sarkar, Ken Okamura, John E. Harris, Johann E. Gudjonsson, Katherine A. Fitzgerald
Summary: The accumulation of cytosolic DNA leads to the production of type I IFNs, maturation of IL-1 cytokines, and pyroptotic cell death. Caspase-1 cleaves pro-IL-1 beta to generate mature cytokines and gasdermin D, which facilitate the release of IL-1 and pyroptotic cell death. AIM2 serves as a sensor for dsDNA, leading to caspase-1 activation, while in human monocytes, cGAS-STING acting upstream of NLRP3 mediates the inflammasome response to dsDNA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Allison C. Billi, Mehrnaz Gharaee-Kermani, Joseph Fullmer, Lam C. Tsoi, Brett D. Hill, Dennis Gruszka, Jessica Ludwig, Xianying Xing, Shannon Estadt, Sonya J. Wolf, Syed Monem Rizvi, Celine C. Berthier, Jeffrey B. Hodgin, Maria A. Reamer, Mrinal K. Sarkar, Yun Liang, Ranjitha Uppala, Shuai Shao, Chang Zeng, Paul W. Harms, Monique E. Verhaegen, John J. Voorhees, Fei Wen, Nicole L. Ward, Andrzej A. Dlugosz, J. Michelle Kahlenberg, Johann E. Gudjonsson