TLR7 activation of age-associated B cells mediates disease in a mouse model of primary Sjögren's disease.

Primary Sjögren's disease (pSD) (also referred to as Sjögren's syndrome) is an autoimmune disease that primarily occurs in women. In addition to exocrine gland dysfunction, pSD patients exhibit B cell hyperactivity. B cell-intrinsic TLR7 activation is integral to the pathogenesis of systemic lupus erythematosus, a disease that shares similarities with pSD.

Compressed 4-day workweek for dental faculty retention and recruitment.

Faculty recruitment and retention are major concerns faced by dental schools across the country. This increase in faculty shortage impacts training the next generation of clinicians and oral health care delivery in dental institutions, which together will exacerbate challenges related to access to dental care. The objective of this paper is to propose a compressed workweek as an incentive to improve recruitment, retention, and faculty well-being.

TLR7 agonism accelerates disease in a mouse model of primary Sjögren's syndrome and drives expansion of T-bet B cells.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by chronic inflammation of exocrine tissue, resulting in loss of tears and saliva. Patients also experience many extra-glandular disease manifestations. Treatment for pSS is palliative, and there are currently no treatments available that target disease etiology.

Mitochondrial ROS production by neutrophils is required for host antimicrobial function against Streptococcus pneumoniae and is controlled by A2B adenosine receptor signaling.

Polymorphonuclear cells (PMNs) control Streptococcus pneumoniae (pneumococcus) infection through various antimicrobial activities. We previously found that reactive oxygen species (ROS) were required for optimal antibacterial function, however, the NADPH oxidase is known to be dispensable for the ability of PMNs to kill pneumococci. In this study, we explored the role of ROS produced by the mitochondria in PMN antimicrobial defense against pneumococci.

Identification of early biomarkers in saliva in genetically engineered mouse model C(3)1-TAg of breast cancer.

Breast cancer is one of leading causes of death worldwide in the female population. Deaths from breast cancer could be reduced significantly through earlier and more efficient detection of the disease. Saliva, an oral fluid that contains an abundance of protein biomarkers, has been recognized as a promising diagnostic biofluid that is easy to isolate through non-invasive techniques.

Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogeneity in Mouse Primary Sjögren's Syndrome Salivary Glands.

Sjögren's Syndrome (SS) is a chronic autoimmune disease of unknown etiology which primarily affects the salivary and lacrimal glands resulting in the loss of secretory function. Treatment options for SS have been hampered due to the lack of a better understanding of the underlying gene regulatory circuitry and the interplay between the myriad pathological cellular states that contribute to salivary gland dysfunction. To better elucidate the molecular nature of SS, we have performed RNA-sequencing analysis of the submandibular glands (SMG) of a well-established primary Sjögren's Syndrome (pSS) mouse model.

Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren's Syndrome.

Primary Sjögren's syndrome is an autoimmune disease that is predominantly seen in women. The disease is characterized by exocrine gland dysfunction in combination with serious systemic manifestations. At present, the causes of pSS are poorly understood.

Tissue-specific activation of Myd88-dependent pathways governs disease severity in primary Sjögren's syndrome.

Myd88 activation is an important driver of autoimmunity. Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by exocrine gland dysfunction in combination with serious systemic disease manifestations. Myd88-dependent signaling networks remain incompletely understood in the context of pSS.

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis.

Activation of Myd88-Dependent TLRs Mediates Local and Systemic Inflammation in a Mouse Model of Primary Sjögren's Syndrome.

Toll-like receptors (TLRs) are important mediators of chronic inflammation in numerous autoimmune diseases, although the role of these receptors in primary Sjögren's syndrome (pSS) remains incompletely understood. Previous studies in our laboratory established Myd88 as a crucial mediator of pSS, although the disease-relevant ligands and the upstream signaling events that culminate in Myd88 activation have yet to be established. The objective of this study was to identify specific Myd88-dependent TLR-related pathways that are dysregulated both locally and systemically in a mouse model of pSS [NOD.

Danger signals in oral cavity-related diseases.

The oral cavity is a unique environment containing teeth juxtaposed with soft tissues, all of which are constantly bathed in microbial products and host-derived factors. While microbial dysbiosis in the oral cavity clearly leads to oral inflammatory disease, recent advances find that endogenous danger-associated molecular patterns (DAMPs) released from oral and salivary tissue also contribute to the progression of inflammatory and autoimmune disease, respectively. In contrast, DAMPs produced during oral fungal infection actually promote the resolution of infection.

Current and Emerging Evidence for Toll-Like Receptor Activation in Sjögren's Syndrome.

While the importance of Toll-like receptor (TLR) signaling is well established in many autoimmune diseases, the role of TLR activation in Sjögren's syndrome (SS) is poorly understood. Studies in mice and humans reveal that TLRs are potent mediators of inflammation in SS. TLRs are expressed and functional in salivary tissue, and TLRs in peripheral blood cells of SS patients are also upregulated and hyperresponsive to ligation.

Myd88 is required for disease development in a primary Sjögren's syndrome mouse model.

Sjögren's syndrome (SS) is an autoimmune disease that often results in diminished exocrine gland function. SS patients also experience systemic disease manifestations, including hypergammaglobulinemia and pulmonary and renal pathoses. MyD88 is a ubiquitously expressed adaptor molecule used by all immune cells that is required for IL-1 receptor (IL-1R), IL-18R, and most TLR signaling.

Clinicopathologic significance of in vivo antinuclear autoantibodies in oral mucosal biopsies.

Objective: Although antinuclear autoantibody (ANA) staining of oral biopsy specimens is indicative of chronic ulcerative stomatitis, it is not known whether this staining is characteristic of other autoimmune diseases. Our study was undertaken to characterize the various in vivo ANA patterns detected in the oral mucosa by direct immunofluorescence to describe the associated hematoxylin and eosin findings, and determine whether patients with these findings had a coexisting systemic connective tissue disease.

Study Design: This was a retrospective analysis of oral biopsy specimens submitted from 2013 to 2016.

Systemic manifestations of primary Sjögren's syndrome in the NOD.B10Sn-H2/J mouse model.

Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.

Fibromyxoma of the Jaw: Case Report and Review of the Literature.

We report a case of fibromyxoma of the mandible, a rare benign odontogenic tumor. Our patient presented in the first trimester of pregnancy with a large mass in the right body of the mandible exhibiting displacement of teeth and destruction of an extensive area of the mandibular bone. The mass was biopsied and diagnosed as a fibromyxoma.

Innate immunity in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease of exocrine tissue that primarily affects women. Although patients typically experience xerostomia and xerophthalmia, numerous systemic disease manifestations are seen. Innate immune hyperactivity is integral to many autoimmune diseases, including SS.

Is it Sjögren's syndrome or burning mouth syndrome? Distinct pathoses with similar oral symptoms.

Sjögren's syndrome (SS) and burning mouth syndrome (BMS) typically occur in postmenopausal women. Although these conditions have significantly different etiopathogeneses, patients with SS or BMS often present with analogous oral complaints. The similarities between the two conditions have led to considerable confusion on the part of medical and dental practitioners, and those with BMS or SS often wait years to receive a diagnosis.

Sera and salivary matrix metalloproteinases are elevated in patients with vesiculoerosive disease: a pilot study.

Background: Oral vesiculoerosive (VE) diseases, such as lichen planus and mucous membrane pemphigoid, are immune-mediated pathoses. Matrix metalloproteinase (MMP)-2 and MMP-9 are elevated in oral lesional biopsy specimens of patients with VE disease. However, the systemic levels and activity of MMP-2 and MMP-9 in this patient population are poorly understood.

Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction.

Sjögren's syndrome (SS) is a debilitating autoimmune disease. Patients with SS may develop xerostomia. This process is progressive, and there are no therapeutics that target disease etiology.

Analysis of IgM antibody production and repertoire in a mouse model of Sjögren's syndrome.

This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjögren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjögren's syndrome mouse model (Id3(-/-)). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells.

T24 HRAS transformed NIH/3T3 mouse cells (GhrasT-NIH/3T3) in serial tumorigenic in vitro/in vivo passages give rise to increasingly aggressive tumorigenic cell lines T1-A and T2-A and metastatic cell lines T3-HA and T4-PA.

Cancer cells often arise progressively from "normal" to "pre-cancer" to "transformed" to "local metastasis" to "metastatic disease" to "aggressive metastatic disease". Recent whole genome sequencing (WGS) and spectral karyotyping (SKY) of cancer cells and tumorigenic models have shown this progression involves three major types of genome rearrangements: ordered small step-wise changes, more dramatic "punctuated evolution" (chromoplexy), and large catastrophic steps (chromothripsis) which all occur in random combinations to generate near infinite numbers of stochastically rearranged metastatic cancer cell genomes. This paper describes a series of mouse cell lines developed sequentially to mimic this type of progression.