Review
Medicine, General & Internal
Yoshiro Horai, Toshimasa Shimizu, Masataka Umeda, Shin-Ya Nishihata, Hideki Nakamura, Atsushi Kawakami
Summary: Sjogren's syndrome is a rheumatic disease characterized by dryness and extraglandular symptoms. Current recommended therapies mainly focus on symptomatic treatment, so a comprehensive approach is needed to understand the pathogenesis and develop disease-specific therapies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Immunology
Shuo Zhang, Jingge Qu, Li Wang, Mengtao Li, Dong Xu, Yan Zhao, Fengchun Zhang, Xiaofeng Zeng
Summary: The upregulation of the TLR7 signaling pathway in B cells of patients with pSS-associated thrombocytopenia may lead to thrombocytopenia, as evidenced by experiments in NOD mice.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Velda X. Han, Hannah F. Jones, Shrujna Patel, Shekeeb S. Mohammad, Markus J. Hofer, Sarah Alshammery, Emma Maple-Brown, Wendy Gold, Fabienne Brilot, Russell C. Dale
Summary: Inflammation plays a significant role in neuro-developmental disorders by affecting neuroimmune signaling in the brain, with maternal and child immune responses to environmental stimuli contributing to aberrations. Toll-like receptors are key innate immune sensors activated by inflammatory factors such as maternal gestational infection, obesity, and stress, potentially leading to offspring neurobehavioral abnormalities.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Chemistry, Medicinal
Yongsheng Zhang, Xinjie Liang, Xuefei Bao, Wei Xiao, Guoliang Chen
Summary: This review discusses TLR4 inhibitors that can bind directly to TLR4 or the TLR4/MD2 complex, as well as compounds that can downregulate the expression of TLR4. The involvement of specific residues in the binding of antagonistic ligands to the TLR4/MD2 complex provides useful information for structure-based TLR4 inhibitor design.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Vadim Mett, Oleg V. Kurnasov, Ivan A. Bespalov, Ivan Molodtsov, Craig M. Brackett, Lyudmila G. Burdelya, Andrei A. Purmal, Anatoli S. Gleiberman, Ilia A. Toshkov, Catherine A. Burkhart, Yakov N. Kogan, Ekaterina L. Andrianova, Andrei V. Gudkov, Andrei L. Osterman
Summary: GP532, a substantially deimmunized derivative of the TLR5 agonist entolimod, retains potent NF-kappa B activation while eliminating key B- and T-cell epitopes and an inflammasome-activating domain. It is suitable for multi-dose therapies and patients with high titers of preexisting flagellin-neutralizing antibodies.
COMMUNICATIONS BIOLOGY
(2021)
Article
Immunology
Jeremy Kiripolsky, Eileen M. Kasperek, Chengsong Zhu, Quan-Zhen Li, Jia Wang, Guan Yu, Jill M. Kramer
Summary: Primary Sjogren's syndrome, predominantly seen in women, is characterized by exocrine gland dysfunction and serious systemic manifestations. Research suggests that ECM degradation may represent a novel source of chronic B cell activation in the context of pSS.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ella A. Zuiderwijk-Sick, Celine van der Putten, Raissa Timmerman, Jennifer Veth, Erica M. Pasini, Linda van Straalen, Paul van der Valk, Sandra Amor, Jeffrey J. Bajramovic
Summary: Exposure to IL-4 induces changes in the cell surface protein expression profile of primary rhesus macaque microglia and enhances their potential to induce proliferation of T cells with a regulatory signature. Additionally, IL-4 exposure broadly impairs TLR-induced cytokine production and inhibits microglial innate immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Rheumatology
Sofie L. M. Blokland, Christina-Maria Flessa, Joel A. G. van Roon, Clio P. Mavragani
Summary: In pSS, chemokines and cytokines play crucial roles in orchestrating immunopathology through regulating a complex network of interacting inflammatory cells. The emerging roles of novel chemotactic and non-chemotactic mediators are highlighted in controlling pathogenic processes, such as promoting B cell hyperactivity and ectopic lymphoid structures formation.
Review
Biochemistry & Molecular Biology
Saahithh Redddi Patlola, Gary Donohoe, Declan P. McKernan
Summary: Toll-like receptors (TLRs) are pattern recognition receptors that protect the brain from self and foreign antigens/pathogens and can elicit a harmful or beneficial immune response. TLR activation has been associated with neurodegenerative diseases and cytokine imbalance in schizophrenia. This review explores the current literature on TLRs, their potential role in schizophrenia pathogenesis, factors affecting TLR activity and their impact on cognitive performance in schizophrenia.
Article
Immunology
Daniela Jara, Patricia Carvajal, Isabel Castro, Maria-Jose Barrera, Sergio Aguilera, Sergio Gonzalez, Claudio Molina, Marcela Hermoso, Maria-Julieta Gonzalez
Summary: Sjogren's syndrome is an autoimmune disease affecting salivary glands with overactivation of the type I interferon pathway. Decreased levels of hsa-miR-145-5p in SS patients lead to upregulation of MUC1 and TLR4, contributing to salivary gland inflammation and dysfunction. Type I interferons play a role in downregulating hsa-miR-145-5p expression, highlighting their involvement in perpetuating inflammation in SS patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Adrienne K. Conger, Toria Tomasek, Kyle J. Riedmann, Joel S. Douglas, Lucia E. Berkey, Lorraine B. Ware, Julie A. Bastarache, Jamie E. Meegan
Summary: Cell-free hemoglobin is involved in endothelial injury during sepsis and ARDS, but the underlying mechanisms remain unclear. In this study, it was found that hemoglobin increased leukocyte adhesion and endothelial activation in HLMVEC through TLR4 signaling, resulting in transcriptional upregulation of inflammatory cytokines and adhesion molecules. Furthermore, hemoglobin-induced NF-κB activation and ROS production were also mediated by TLR4.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Rheumatology
Robert I. Fox, Carla M. Fox, Jacques Eric Gottenberg, Thomas Doerner
Summary: SS is characterized by severe fatigue, dryness, pain, glandular swelling, and various systemic manifestations. Clinical trials have failed due to lack of extraglandular symptoms in enrolled patients. Future therapies should focus on improving symptoms and exploring innovative treatment directions.
Article
Clinical Neurology
Pinku Mani Talukdar, Fazal Abdul, Michael Maes, Michael Berk, Ganesan Venkatasubramanian, Bindu M. Kutty, Monojit Debnath
Summary: Prenatal infection-induced maternal immune activation (MIA) may trigger TLR and inflammasome pathways, increasing the risk of schizophrenia-like behaviors in the offspring later in life.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mojca Jensterle, Rok Herman, Andrej Janez
Summary: Despite lifestyle intervention and symptomatic management being the main treatments for PCOS, GLP-1 receptor agonists have shown superior weight loss effects and additional metabolic, reproductive, and cardiovascular benefits compared to other treatments. However, concerns about contraception and washout periods before pregnancy have limited their acceptance in the clinical community treating PCOS.
Review
Biochemistry & Molecular Biology
Toshimasa Shimizu, Hideki Nakamura, Atsushi Kawakami
Summary: Sjogren's syndrome is a systemic autoimmune disease characterized by chronic inflammation, involving adaptive immune response and type I interferon signature. Innate immune responses play a role in the pathogenesis of Sjogren's syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Jason G. Kay, Jill M. Kramer, Michelle B. Visser
JOURNAL OF LEUKOCYTE BIOLOGY
(2019)
Article
Dentistry, Oral Surgery & Medicine
A. Oyelakin, E. A. C. Song, S. Min, J. E. Bard, J. Kann, E. Horeth, K. Smalley, J. M. Kramer, S. Sinha, R. A. Romano
JOURNAL OF DENTAL RESEARCH
(2019)
Article
Immunology
Jeremy Kiripolsky, Rose-Anne Romano, Eileen M. Kasperek, Guan Yu, Jill M. Kramer
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Akinsola Oyelakin, Erich Horeth, Eun-Ah Christine Song, Sangwon Min, Monika Che, Brandon Marzullo, Christopher J. Lessard, Astrid Rasmussen, Lida Radfar, R. Hal Scofield, David M. Lewis, Donald U. Stone, Kiely Grundahl, Scott S. De Rossi, Zoya Kurago, A. Darise Farris, Kathy L. Sivils, Satrajit Sinha, Jill M. Kramer, Rose-Anne Romano
Summary: Primary Sjogren's syndrome is a systemic autoimmune disease primarily affecting women, leading to loss of saliva and tears. Currently, there is no effective cure due to limited understanding of disease etiology and pathology.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jeremy Kiripolsky, Eileen M. Kasperek, Chengsong Zhu, Quan-Zhen Li, Jia Wang, Guan Yu, Jill M. Kramer
Summary: Myd88 activation plays a crucial role in specific cell types in the pathology of pSS. Deleting Myd88 in hematopoietic cells can mitigate inflammatory responses in salivary tissue and nephritis, but increases pulmonary inflammation; meanwhile, ablation of Myd88 in stromal cells can reduce pulmonary inflammation and alleviate levels of anti-nuclear autoantibodies.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Immunology
Jeremy Kiripolsky, Eileen M. Kasperek, Chengsong Zhu, Quan-Zhen Li, Jia Wang, Guan Yu, Jill M. Kramer
Summary: Primary Sjogren's syndrome, predominantly seen in women, is characterized by exocrine gland dysfunction and serious systemic manifestations. Research suggests that ECM degradation may represent a novel source of chronic B cell activation in the context of pSS.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Erich Horeth, Akinsola Oyelakin, Eun-Ah Christine Song, Monika Che, Jonathan Bard, Sangwon Min, Jeremy Kiripolsky, Jill M. Kramer, Satrajit Sinha, Rose-Anne Romano
Summary: Sjogren's Syndrome is a chronic autoimmune disease affecting salivary and lacrimal glands. RNA sequencing and single-cell RNA sequencing have revealed important pathways and regulatory networks in the pathobiology of SS, as well as the diversity in activated state of salivary gland epithelial cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Isadora Fernandes Gilson Sena, Larissa Lessi Fernandes, Leonardo Lima Lorandi, Thais Viggiani Santana, Luciana Cintra, Ismael Feitosa Lima, Leo Kei Iwai, Jill M. Kramer, Alexander Birbrair, Debora Heller
Summary: Breast cancer is a leading cause of death in women worldwide. Detecting the disease earlier and more efficiently could significantly reduce mortality rates. Saliva, an easy-to-isolate and non-invasive biofluid, has been recognized as a promising diagnostic tool due to its abundance of protein biomarkers. This study aimed to identify salivary biomarkers in the initial stages of breast cancer, before histopathological analysis can detect cell alterations. By analyzing proteins in saliva from a transgenic mouse model of mammary cancer, we found molecular changes related to metabolic, inflammatory, and cellular matrix degradation processes at the onset of tumor development. Our work demonstrated that salivary protein profiles can non-invasively identify cellular changes associated with precancerous breast cancer.
SCIENTIFIC REPORTS
(2022)
Article
Dentistry, Oral Surgery & Medicine
E. Horeth, J. Bard, M. Che, T. Wrynn, E. A. C. Song, B. Marzullo, M. S. Burke, S. Popat, T. Loree, J. Zemer, J. L. Tapia, J. Frustino, J. M. Kramer, S. Sinha, R. A. Romano
Summary: This study comprehensively characterizes the molecular features and expression profiles of human submandibular gland cells using single-cell and bulk RNA sequencing. It reveals a variety of cell types and provides insights into cell-cell communication and the dynamic process of differentiation.
JOURNAL OF DENTAL RESEARCH
(2023)
Article
Microbiology
Sydney E. Herring, Sovathiro Mao, Manmeet Bhalla, Essi Y. Tchalla, Jill M. Kramer, Elsa N. Bou Ghanem
Summary: This study reveals that polymorphonuclear cells (PMNs) control Streptococcus pneumoniae infection through the production of reactive oxygen species (ROS) by mitochondria. The production of mitochondrial ROS (MitROS) is independent of bacterial capsule or pneumolysin, but is enhanced by the presence of live bacteria in direct contact with PMNs. The host A2B adenosine receptor inhibits the production of MitROS by PMNs. MitROS are required for PMNs to kill pneumococci and for host resistance against S. pneumoniae infection.
Article
Immunology
Achamaporn Punnanitinont, Eileen M. Kasperek, Jeremy Kiripolsky, Chengsong Zhu, Jeffrey C. Miecznikowski, Jill M. Kramer
Summary: Activation of TLR7 accelerates the pathogenesis of pSS, leading to exacerbation of local and systemic disease, as well as expansion of T-bet-expressing B cells in pSS.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Dentistry, Oral Surgery & Medicine
Fatemeh S. S. Afshari, Leticia Guajardo, Jill M. M. Kramer, Ammar Musawi, Shankar Regasamy Venugopalan, Anita Sykes-Smith
Summary: This article proposes the implementation of a compressed workweek in dental institutions to address the faculty shortage issue and improve recruitment, retention, and employee well-being. The 4-day workweek has been shown to have benefits such as increased job satisfaction, reduced absenteeism, and improved mental health. It is recommended as a solution to attract recent graduates to academia and retain clinical instructors.
JOURNAL OF DENTAL EDUCATION
(2023)
Review
Dentistry, Oral Surgery & Medicine
Achamaporn Punnanitinont, Jill M. Kramer
Summary: Many autoimmune diseases, including primary Sjogren's disease (pSD), have a higher prevalence in females. pSD patients show exocrine gland pathology and various systemic manifestations. Recent studies have uncovered the regulatory mechanisms that contribute to female susceptibility to autoimmunity, including sex hormones, genetic alterations, and the role of gut microbiota. Therapeutics targeting sex-specific inflammatory signaling networks are being explored in clinical trials for pSD.
FRONTIERS IN DENTAL MEDICINE
(2023)
Article
Pathology
Hattan Zaki, Amarpreet Sabharwal, Jill Kramer, Alfredo Aguirre
HEAD & NECK PATHOLOGY
(2019)
Meeting Abstract
Immunology
Jeremy Kiripolsky, Eileen M. Kasperek, Guan Yu, Jill M. Kramer
JOURNAL OF IMMUNOLOGY
(2019)