Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression

Training during the COVID-19 lockdown : knowledge, beliefs, and practices of 12,526 athletes from 142 countries and six continents

OBJECTIVE Our objective was to explore the training-related knowledge, beliefs, and practices of athletes and the influence of lockdowns in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS Athletes (n = 12,526, comprising 13% world class, 21% international, 36% national, 24% state, and 6% recreational) completed an online survey that was available from 17 May to 5 July 2020 and explored their training behaviors (training knowledge, beliefs/attitudes, and practices), including specific questions on their training intensity, frequency, and session duration before and during lockdown (March–June 2020). RESULTS Overall, 85% of athletes wanted to “maintain training,” and 79% disagreed with the statement that it is “okay to not train during lockdown,” with a greater prevalence for both in higher-level athletes. In total, 60% of athletes considered “coaching by correspondence (remote coaching)” to be sufficient (highest amongst world-class athletes). During lockdown, < 40% were able to maintain sport-specific training (e.g., long endurance [39%], interval training [35%], weightlifting [33%], most (83%) training for “general fitness and health maintenance” during lockdown. Athletes trained alone (80%) and focused on bodyweight (65%) and cardiovascular (59%) exercise/training during lockdown. Compared with before lockdown, most athletes reported reduced training frequency (from between five and seven sessions per week to four or fewer), shorter training sessions (from ≥ 60 to < 60 min), and lower sport-specific intensity (~ 38% reduction), irrespective of athlete classification. CONCLUSIONS COVID-19-related lockdowns saw marked reductions in athletic training specificity, intensity, frequency, and duration, with notable within-sample differences (by athlete classification). Higher classification athletes had the strongest desire to “maintain” training and the greatest opposition to “not training” during lockdowns. These higher classification athletes retained training specificity to a greater degree than others, probably because of preferential access to limited training resources. More higher classification athletes considered “coaching by correspondence” as sufficient than did lower classification athletes. These lockdown-mediated changes in training were not conducive to maintenance or progression of athletes’ physical capacities and were also likely detrimental to athletes’ mental health. These data can be used by policy makers, athletes, and their multidisciplinary teams to modulate their practice, with a degree of individualization, in the current and continued pandemic-related scenario. Furthermore, the data may drive training-related educational resources for athletes and their multidisciplinary teams. Such upskilling would provide athletes with evidence to inform their training modifications in response to germane situations (e.g., COVID related, injury, and illness).A specific funding was provided by the National Sports Institute of Malaysia for this study.The National Sports Institute of Malaysia.https://www.springer.com/journal/40279am2023Sports Medicin

COVID-19 lockdown : a global study investigating athletes’ sport classification and sex on training practices

PURPOSE : To investigate differences in athletes’ knowledge, beliefs, and training practices during COVID-19 lockdowns with reference to sport classification and sex. This work extends an initial descriptive evaluation focusing on athlete classification. METHODS : Athletes (12,526; 66% male; 142 countries) completed an online survey (May–July 2020) assessing knowledge, beliefs, and practices toward training. Sports were classified as team sports (45%), endurance (20%), power/technical (10%), combat (9%), aquatic (6%), recreational (4%), racquet (3%), precision (2%), parasports (1%), and others (1%). Further analysis by sex was performed. RESULTS : During lockdown, athletes practiced body-weight-based exercises routinely (67% females and 64% males), ranging from 50% (precision) to 78% (parasports). More sport-specific technical skills were performed in combat, parasports, and precision (∼50%) than other sports (∼35%). Most athletes (range: 50% [parasports] to 75% [endurance]) performed cardiorespiratory training (trivial sex differences). Compared to prelockdown, perceived training intensity was reduced by 29% to 41%, depending on sport (largest decline: ∼38% in team sports, unaffected by sex). Some athletes (range: 7%–49%) maintained their training intensity for strength, endurance, speed, plyometric, change-of-direction, and technical training. Athletes who previously trained ≥5 sessions per week reduced their volume (range: 18%–28%) during lockdown. The proportion of athletes (81%) training ≥60 min/session reduced by 31% to 43% during lockdown. Males and females had comparable moderate levels of training knowledge (56% vs 58%) and beliefs/attitudes (54% vs 56%). CONCLUSIONS : Changes in athletes’ training practices were sport-specific, with few or no sex differences. Team-based sports were generally more susceptible to changes than individual sports. Policy makers should provide athletes with specific training arrangements and educational resources to facilitate remote and/or home-based training during lockdown-type events.https://journals.humankinetics.com/view/journals/ijspp/ijspp-overview.xmlhj2023Sports Medicin

Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins

Objective. Exosomes are membrane vesicles of endosomal origin that are distinct from apoptotic bodies and are thought to represent an a cellular mechanism for antigen transfer to classic antigen-presenting cells, as well as for direct antigen presentation with the capacity to induce immune response or tolerance. Nevertheless, it is not known whether exosomes are involved in the induction or regulation of immune responses against intracellular autoantigens that characterize autoimmune diseases. Exosomes have been shown to be secreted by several types of cells, whereas studies of non-neoplastic epithelial cells are lacking. This study was undertaken to investigate the capacity of non-neoplastic salivary gland epithelial cells (SGECs) to release exosomes, and to determine whether epithelial exosomes contain RNPs, which are major autoantigens in systemic rheumatic diseases. Methods. Exosomes were isolated by ultracentrifugation from culture supernatants of 26 non-neoplastic SGEC lines established from patients with various rheumatic disorders. They were analyzed by electron microscopy, immunoblotting, or immunoprecipitation. Results. All SGEC lines were found to release comparable and significant amounts of exosomes. Similar to other cell systems, exosome secretion was constitutive and was unrelated to activation or apoptotic processes. SGEC-derived exosomes were found to contain the autoantigenic Ro/SSA, La/SSB, and Sm RNPs, as well as epithelial-specific cryptographist. Conclusion. SGECs constitutively secrete exosomes that contain the major autoantigens Ro/SSA, La/SSB, and Sm. This mechanism may represent a pathway whereby intracellular autoantigens are presented to the immune system with an immunogenic or tolerogenic outcome. © 2005, American College of Rheumatology

Establishment of a convenient system for the long-term culture and study of non-neoplastic human salivary gland epithelial cells.

Epithelial cells appear to play an important role in the initiation and maintenance of autoimmune lesions in the salivary glands of patients with Sjogren&apos;s syndrome. Therefore, the detailed study of immunological function of salivary gland epithelial cells (SGEC) may provide useful information for the understanding of Sjögren&apos;s syndrome pathogenesis. In this report we aimed to formulate a protocol for the establishment of human non-neoplastic SGEC lines as a tool for the study of the physiology and pathophysiology of these cells. Pointing towards a practical approach, we sought to establish SGEC lines from quite a limited amount of biopsy tissue obtained during the diagnostic evaluation of patients. Herein, the favorable conditions for the long-term maintenance of human non-neoplastic SGEC lines are presented and involve the successive application of a serum-containing and a serum-free culture medium, supplemented with essential epithelial growth factors. This protocol has been found reliable and convenient, as attested by the reproducible establishment of non-neoplastic SGEC lines. The analysis of SGEC phenotypic features, as well as a coculture system for the study of interactions between epithelial cells and lymphocytes, are also described. Such techniques may provide valuable means for the functional and molecular investigation of human SGEC and particularly for the study of Sjögren&apos;s syndrome and other disorders of glandular epithelia