Review
Immunology
Samuel Lara-Reyna, Emily A. Caseley, Joanne Topping, Francois Rodrigues, Jorge Jimenez Macias, Sean E. Lawler, Michael F. McDermott
Summary: Inflammasomes are innate immune sensors assembled by cells to detect danger signals and initiate pro-inflammatory responses. They activate inflammatory caspases, leading to cellular damage and release of pro-inflammatory cytokines. Multiple molecular mechanisms regulate inflammasome activation to maintain a balance between inflammation and tissue integrity. Aberrant inflammasome activation can result in excessive production of pro-inflammatory cytokines and cell death, causing tissue damage.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)
Review
Immunology
Hanae Miyazawa, Taizo Wada
Summary: This review discusses recent findings in inflammatory diseases associated with chronic excess of serum IL-18 and describes the clinical and therapeutic relevance of understanding the pathology of this group of diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Fang Liang, Weixiao Qin, Yilan Zeng, Dan Wang
Summary: Autoimmune diseases and autoinflammatory diseases are two types of immune system disorders, and pyroptosis plays a crucial role in these diseases. Gasdermins, a pore-forming protein mainly expressed in immune cells, gastrointestinal tract, and skin, are considered as the executors of pyroptosis and have various functions and pathological effects such as pro-inflammatory responses, immune activation, and tumor mediation. Recent studies have demonstrated the significant role of gasdermins in autoimmune diseases, autoinflammatory diseases, and immune-related neoplastic diseases, making them potential therapeutic targets for immune disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Wenjie Zheng, Xiaorui Fan, Zhaohui Yang, Yaoyao Shangguan, Taijie Jin, Yan Liu, Jiqian Huang, Xiaohua Ye, Qing Zhou, Xiaozhong Li
Summary: This study aimed to investigate the potential role of neutrophils and inflammatory signatures in the pathogenesis of PAMI syndrome. The results showed that PAMI neutrophils displayed increased production of IL-1β and IL-18, along with increased pyrin inflammasome activation and upregulated NF-κB and IFN signaling pathways. These findings suggest the important roles of neutrophils in the pathogenicity of PAMI syndrome.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Carl Christoph Goetzke, Frederic Ebstein, Tilmann Kallinich
Summary: The UPS plays a crucial role in cellular functions, such as regulating protein homeostasis and MHC I antigen processing. In humans, loss-of-function mutations in the proteasome can lead to autoinflammation, while abnormally increased proteasomal activity is also linked to other inflammatory diseases.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Asami Watahiki, Seira Hoshikawa, Mitsuki Chiba, Hiroshi Egusa, Satoshi Fukumoto, Hiroyuki Inuzuka
Summary: This study elucidated the molecular link between lipin2 deficiency and the development of autoinflammatory bone disorder, showing that lipin2 suppresses inflammatory responses and osteoclastogenesis in macrophages. The findings suggest that lipin2 plays a critical role in regulating immune responses and bone metabolism, offering potential therapeutic insights for monogenic autoinflammatory bone disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Simon Bossart, S. Morteza Seyed Jafari, Kristine Heidemeyer, Kexiang Yan, Laurence Feldmeyer, Luca Borradori, Nikhil Yawalkar
Summary: IL-1-blocking therapies have shown effectiveness in reducing disease severity and inflammation in Schnitzler syndrome. In this study, a patient with Schnitzler syndrome was successfully treated with canakinumab for over 10 years. Complete clinical response was observed, along with a decrease in dermal neutrophil number and the expression of pro-inflammatory cytokines IL-1 beta, IL-8, and IL-17.
FRONTIERS IN MEDICINE
(2023)
Article
Medicine, General & Internal
Juliette Bardet, Noemie Laverdure, Mathieu Fusaro, Capucine Picard, Lorna Garnier, Sebastien Viel, Sophie Collardeau-Frachon, Jean-Marie De Guillebon, Isabelle Durieu, Clemence Casari-Thery, Guillaume Mortamet, Audrey Laurent, Alexandre Belot
Summary: NLRC4 inflammasome, a part of human innate immune system, is associated with diverse clinical manifestations and limited genotype-phenotype correlations. Patients may present with gastrointestinal symptoms and vasoplegic shock, requiring plasma IL-18 level and genetic screening for final diagnosis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
Wei-Sheng Lin, Ting-Rong Hsu
Summary: FIRES is a protracted neuroinflammatory condition of unknown cause that mainly affects school-age children and often leads to permanent neurological sequelae. Limited efficacy of current treatments and the rarity and complexity of the syndrome hamper research. Microglia and the NLRP3 inflammasome are suggested to play pivotal roles in the pathogenesis of FIRES.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Article
Immunology
Annemarie Steiner, Thomas Reygaerts, Alessandra Pontillo, Isabella Ceccherini, Jonas Moecking, Fiona Moghaddas, Sophia Davidson, Francesco Caroli, Alice Grossi, Fabio Fernandes Morato Castro, Jorge Kalil, Florian N. Gohr, Florian Schmidt, Eva Bartok, Thomas Zillinger, Gunther Hartmann, Matthias Geyer, Marco Gattorno, Leonardo Oliveira Mendonca, Seth L. Masters
Summary: NLRC4 (A160T) can lead to recessively inherited autoinflammation and immune dysregulation, or function as a heterozygous risk factor for the development of ulcerative colitis.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Review
Immunology
Tomohiro Koga, Atsushi Kawakami
Summary: IL-6 plays an important role in autoinflammatory diseases and is considered a promising therapeutic target.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Zhihao Xu, Shasha Deng, Yuluo Huang, Yunru Yang, Liangqi Sun, Hanyuan Liu, Dan Zhao, Weihong Zeng, Xueying Yin, Peiyi Zheng, Yingying Wang, Muziying Liu, Weidong Zhao, Tsan Sam Xiao, Ying Zhou, Tengchuan Jin
Summary: This study elucidates the regulation of NLRP1 inflammasome activation by CARD8 and provides insights into the assembly mechanisms of CARD-containing inflammasomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Akhouri Kishore Raghawan, Rajashree Ramaswamy, Ghanshyam Swarup
Summary: NLRP3 is a cytoplasmic receptor protein that initiates an inflammatory immune response. Mutations in NLRP3 cause a hereditary disorder called familial cold autoinflammatory syndrome-1 (FCAS1). This study found that NLRP3 interacts with HSC70 and this interaction suppresses inflammasome formation. Exposure to subnormal temperature reduces this interaction and leads to increased inflammasome formation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Immunology
Yuhua Shi, Qian Lv, Mengjie Zheng, Hongxiang Sun, Fushan Shi
Summary: INF39 is a specific inhibitor for NLRP3 inflammasome activation, without affecting other inflammasomes. It exerts its anti-inflammatory effect by inhibiting the interaction of NEK7-NLRP3 and other downstream events.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Genetics & Heredity
Hui Hui Wong, Sze Hwee Seet, Michael Maier, Ayse Gurel, Ricardo Moreno Traspas, Cheryl Lee, Shan Zhang, Beril Talim, Abigail Y. T. Loh, Crystal Y. Chia, Tze Shin Teoh, Danielle Sng, Jarred Rensvold, Sule Unal, Evgenia Shishkova, Ece Cepni, Fatima M. Nathan, Fernanda L. Sirota, Chao Liang, Nese Yarali, Pelin O. Simsek-Kiper, Tadahiro Mitani, Serdar Ceylaner, Ozlem Arman-Bilir, Hamdi Mbarek, Fatma Gumruk, Stephanie Efthymiou, Deniz Ugurlu Cimen, Danai Georgiadou, Kortessa Sotiropoulou, Henry Houlden, Franziska Paul, Davut Pehlivan, Candice Laine, Guoliang Chai, Nur Ain Ali, Siew Chin Choo, Soh Sok Keng, Bertrand Boisson, Elanur Yilmaz, Shifeng Xue, Joshua J. Coon, Thanh Thao Nguyen Ly, Naser Gilani, Dana Hasbini, Hulya Kayserili, Maha S. Zaki, Robert J. Isfort, Natalia Ordonez, Kornelia Tripolszki, Peter Bauer, Nima Rezaei, Simin Seyedpour, Ghamar Taj Khotaei, Charles C. Bascom, Reza Maroofian, Myriam Chaabouni, Afaf Alsubhi, Wafaa Eyaid, Sedat Isikay, Joseph G. Gleeson, James R. Lupski, Jean-Laurent Casanova, David J. Pagliarini, Nurten A. Akarsu, Sebastian Maurer-Stroh, Arda Cetinkaya, Aida Bertoli-Avella, Ajay S. Mathuru, Lena Ho, Frederic A. Bard, Bruno Reversade
Summary: This study identifies an autosomal recessive disorder caused by C2orf69 deficiency, which disrupts the immune and central nervous systems' development and homeostasis.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Immunology
Rajendra Karki, SangJoon Lee, Raghvendra Mall, Nagakannan Pandian, Yaqiu Wang, Bhesh Raj Sharma, Rk Subbarao Malireddi, Dong Yang, Sanja Trifkovic, Jacob A. Steele, Jon P. Connelly, Gella Vishwanath, Mitnala Sasikala, Duvvur Nageshwar Reddy, Peter Vogel, Shondra M. Pruett-Miller, Richard Webby, Colleen Beth Jonsson, Thirumala-Devi Kanneganti
Summary: This study found that ZBP1 induced during coronavirus infection limits the efficacy of IFN therapy by driving inflammatory cell death and lethality. Inhibiting ZBP1 activity may improve the efficacy of IFN therapy for COVID-19 and other infections and inflammatory conditions where IFN-mediated cell death and pathology occur.
SCIENCE IMMUNOLOGY
(2022)
Review
Cell Biology
Yetirajam Rajesh, Thirumala-Devi Kanneganti
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by the formation of plaques and abnormalities in certain proteins. Immune cells play a crucial role in the development of the disease, as they can cause cell death and release proinflammatory cytokines. However, chronic inflammation can worsen the condition. Therefore, balancing the immune response is important for effectively clearing the abnormal proteins without inducing inflammation.
Review
Medical Laboratory Technology
Bhesh Raj Sharma, Thirumala-Devi Kanneganti
Summary: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, with inflammation being a key risk factor. Inflammasomes, multiprotein immune complexes, play a crucial role in maintaining gut homeostasis and regulating inflammation. They have been shown to be involved in colitis and colitis-associated CRC, through the release of interleukin-1 beta and IL-18. Different inflammasome sensors provide protection against colitis-associated CRC through both effector cytokine-dependent and -independent mechanisms. Inflammasomes also contribute to PANoptosomes and PANoptosis, which are forms of innate immune inflammatory cell death. Understanding the mechanisms and functions of inflammasomes in CRC could lead to potential therapeutic targets.
TRANSLATIONAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Camila Marques-da-Silva, Barun Poudel, Rodrigo P. Baptista, Kristen Peissig, Lisa S. Hancox, Justine C. Shiau, Lecia L. Pewe, Melanie J. Shears, Thirumala-Devi Kanneganti, Photini Sinnis, Dennis E. Kyle, Prajwal Gurung, John T. Harty, Samarchith P. Kurup
Summary: Malaria, caused by Plasmodium parasites, is a severe disease affecting millions of people worldwide. The researchers have discovered a pathway of natural immunity critical for the control of malaria in the liver, which involves the sensing of Plasmodium DNA by cytosolic AIM2 receptors in infected hepatocytes, leading to Caspase-1 activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Rajendra Karki, Thirumala-Devi Kanneganti
Summary: ADAR1 and ZBP1 are two mammalian proteins with Z alpha domains that bind to nucleic acids. They play crucial roles in regulating various biological processes. Recent studies have expanded our understanding of their functions, establishing their fundamental regulation of innate immune responses. This review discusses their roles in innate immune responses in development and disease.
TRENDS IN IMMUNOLOGY
(2023)
Article
Microbiology
Shishir Singh, Mateo Murillo-Leon, Niklas Sebastian Endres, Ailan Farid Arenas Soto, Jorge Enrique Gomez-Marin, Florence Melbert, Thirumala-Devi Kanneganti, Masahiro Yamamoto, Claudia Campos, Jonathan Charles Howard, Gregory Alan Taylor, Tobias Steinfeldt
Summary: Toxoplasmosis is a common parasitic zoonosis caused by Toxoplasma gondii, which infects virtually all warm-blooded animals including humans. This study identifies a virulence effector, ROP39, in T. gondii that specifically targets Irgb10 to evade IRG-mediated control, increasing its pathogenicity. This finding contributes to our understanding of the coevolutionary relationship between T. gondii and mice, which are important for transmission.
Article
Multidisciplinary Sciences
Joo-Hui Han, Rebecca E. Tweedell, Thirumala-Devi Kanneganti
Summary: Innate immunity is the first line of defense against pathogens and sterile insults. Understanding the activation and regulation of innate immune programmed cell death (PCD) is crucial for characterizing immune responses and identifying therapeutic targets across diseases.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Multidisciplinary Sciences
Lalita Mazgaeen, Matthew Yorek, Saurabh Saini, Peter Vogel, David K. Meyerholz, Thirumala-Devi Kanneganti, Prajwal Gurung
Summary: Mice with a specific amino acid substitution in SHP1 protein (Ptpn6(spin) mice) develop an autoinflammatory disease. When Ptpn6(spin) bone marrow cells are transferred into Cd47-deficient mice, marked weight loss and death occur. The study suggests that gut leakage caused by pathogenic neutrophils may contribute to the morbidity and mortality in Cd47(-/-) mice receiving Ptpn6(spin) cells. IL-1 blockade with anakinra can rescue the disease phenotype.
Review
Immunology
Wen Chen, Jessica M. M. Gullett, Rebecca E. E. Tweedell, Thirumala-Devi Kanneganti
Summary: Regulated cell death (RCD) is important for host survival during pathogen invasion and cellular disturbances. This review focuses on the newly discovered RCD pathway called PANoptosis, which is an inflammatory cell death pathway regulated by PANoptosome complexes. The article discusses the molecular components of PANoptosomes, their assembly, activation, regulation, and their link to diseases.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Rebecca E. Tweedell, Sivakumar Prasanth Kumar, Thirumala-Devi Kanneganti
Summary: The past two decades of research have revealed new innate immune sensing and cell death pathways that are relevant to diseases. Further molecular characterization of these pathways and understanding their crosstalk and functional redundancies will contribute to the development of therapeutic strategies.
Article
Multidisciplinary Sciences
R. K. Subbarao Malireddi, Ratnakar R. Bynigeri, Raghvendra Mall, Eswar Kumar Nadendla, Jon P. Connelly, Shondra M. Pruett-Miller, Thirumala-Devi Kanneganti
Summary: Transforming growth factor-beta-activated kinase 1 (TAK1) is a central regulator of innate immunity, cell death, inflammation, and cellular homeostasis. Many pathogens carry TAK1 inhibitors (TAK1i), but inhibition or deletion of TAK1 induces spontaneous inflammatory cell death, PANoptosis, which promotes pathological inflammation. Therefore, understanding the molecular mechanisms that regulate TAK1i-induced cell death is crucial.
Article
Virology
R. K. Subbarao Malireddi, Bhesh Raj Sharma, Ratnakar R. Bynigeri, Yaqiu Wang, Jianlin Lu, Thirumala-Devi Kanneganti
Summary: This study investigates the role of MLKL in regulating IAV-induced cell death and NLRP3 inflammasome activation. The results indicate that IAV induces inflammatory cell death through the ZBP1-PANoptosome, partially dependent on RIPK3 at later timepoints and independent of MLKL throughout all timepoints. Additionally, NLRP3 inflammasome activation is unaffected in MLKL-deficient cells, suggesting that MLKL and MLKL-dependent necroptosis do not act upstream of NLRP3 inflammasome activation, IL-1 beta maturation, and lytic cell death during IAV infection.
Editorial Material
Oncology
Rebecca E. Tweedell, Thirumala-Devi Kanneganti
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biology
R. K. Subbarao Malireddi, Ratnakar R. Bynigeri, Raghvendra Mall, Jon P. Connelly, Shondra M. Pruett-Miller, Thirumala-Devi Kanneganti
Summary: This study utilized a genome-wide screening approach to identify host factors and cellular death mechanisms associated with beta-coronavirus infection. The findings revealed key factors involved in innate immune processes and provided new targets for therapeutic development against beta-coronavirus infections.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Wen Chen, Thirumala-Devi Kanneganti
