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Rheumatology and Therapy Sep 2021Sjögren's syndrome (SS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This leads to dryness of the main mucosal... (Review)
Review
Sjögren's syndrome (SS) is a systemic autoimmune disease, characterized by lymphocytic infiltration of the secretory glands. This leads to dryness of the main mucosal surfaces such as the mouth, eyes, nose, larynx, pharynx, and vagina. Although there is little morbidity data at the initial diagnosis, SS may be a serious disease, with extra mortality caused by hematological cancer. The cause of SS is unknown, but factors postulated to play a role include genetic and environmental factors, hormonal abnormality, and viral infection. Under the influence of these factors, the immune system becomes abnormal and the tissue is damaged. In this study, we summarize recent developments in our understanding of the relationship between SS and viral infections, including Epstein-Barr virus (EBV), hepatitis C virus (HCV), human T cell lymphotropic virus type 1 (HTLV-1), cytomegalovirus (CMV), and human immunodeficiency virus (HIV).
PubMed: 34227038
DOI: 10.1007/s40744-021-00334-8 -
Nature Immunology Jul 2023Fibroblastic reticular cells (FRCs) direct the interaction and activation of immune cells in discrete microenvironments of lymphoid organs. Despite their important role...
Fibroblastic reticular cells (FRCs) direct the interaction and activation of immune cells in discrete microenvironments of lymphoid organs. Despite their important role in steering innate and adaptive immunity, the age- and inflammation-associated changes in the molecular identity and functional properties of human FRCs have remained largely unknown. Here, we show that human tonsillar FRCs undergo dynamic reprogramming during life and respond vigorously to inflammatory perturbation in comparison to other stromal cell types. The peptidase inhibitor 16 (PI16)-expressing reticular cell (PI16 RC) subset of adult tonsils exhibited the strongest inflammation-associated structural remodeling. Interactome analysis combined with ex vivo and in vitro validation revealed that T cell activity within subepithelial niches is controlled by distinct molecular pathways during PI16 RC-lymphocyte interaction. In sum, the topological and molecular definition of the human tonsillar stromal cell landscape reveals PI16 RCs as a specialized FRC niche at the core of mucosal immune responses in the oropharynx.
Topics: Humans; T-Lymphocytes; Palatine Tonsil; Fibroblasts; Lymphocytes; Inflammation; Carrier Proteins; Glycoproteins
PubMed: 37202490
DOI: 10.1038/s41590-023-01502-4 -
Cell Sep 2021SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain...
SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1 goblet, and KRT13 "hillock"-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.
Topics: Adult; Aged; Bystander Effect; COVID-19; Cohort Studies; Female; Humans; Immunity; Male; Middle Aged; Nasopharynx; RNA, Viral; Respiratory Mucosa; SARS-CoV-2; Severity of Illness Index; Transcription, Genetic; Viral Load
PubMed: 34352228
DOI: 10.1016/j.cell.2021.07.023 -
Developmental and Comparative Immunology Aug 2021Immunoglobulins (Igs) are complex glycoproteins that play critical functions in innate and adaptive immunity of all jawed vertebrates. Given the unique characteristics... (Review)
Review
Immunoglobulins (Igs) are complex glycoproteins that play critical functions in innate and adaptive immunity of all jawed vertebrates. Given the unique characteristics of mucosal barriers, secretory Igs (sIgs) have specialized to maintain homeostasis and keep pathogens at bay at mucosal tissues from fish to mammals. In teleost fish, the three main IgH isotypes, IgM, IgD and IgT/Z can be found in different proportions at the mucosal secretions of the skin, gills, gut, nasal, buccal, and pharyngeal mucosae. Similar to the role of mammalian IgA, IgT plays a predominant role in fish mucosal immunity. Recent studies in IgT have illuminated the primordial role of sIgs in both microbiota homeostasis and pathogen control at mucosal sites. Ten years ago, IgT was discovered to be an immunoglobulin class specialized in mucosal immunity. Aiming at this 10-year anniversary, the goal of this review is to summarize the current status of the field of fish Igs since that discovery, while identifying knowledge gaps and future avenues that will move the field forward in both basic and applied science areas.
Topics: Animals; Fish Diseases; Fish Proteins; Fishes; Immunity, Mucosal; Immunoglobulins; Lymphoid Tissue; Mucous Membrane; Vaccination
PubMed: 33785432
DOI: 10.1016/j.dci.2021.104079 -
Psychosocial Oncology: Optimizing Outcomes through Interdisciplinary Care in Head and Neck Oncology.Current Oncology (Toronto, Ont.) Jul 2023Head and neck squamous cell carcinomas arise from the mucosal epithelium of the oral cavity (lips, buccal mucosa, anterior tongue, hard palate, floor of mouth, and...
Head and neck squamous cell carcinomas arise from the mucosal epithelium of the oral cavity (lips, buccal mucosa, anterior tongue, hard palate, floor of mouth, and retromolar trigone), nasopharynx, oropharynx (tonsils, base of tongue, soft palate, uvula, and posterior pharyngeal wall), hypopharynx, and larynx [...].
Topics: Humans; Psycho-Oncology; Tongue; Squamous Cell Carcinoma of Head and Neck; Medical Oncology; Head and Neck Neoplasms
PubMed: 37504361
DOI: 10.3390/curroncol30070501 -
Ear, Nose, & Throat Journal Jul 2020
Topics: Cheek; Diagnosis, Differential; Female; Humans; Medical Illustration; Middle Aged; Mucositis; Palate, Soft; Pharyngeal Diseases; Pharynx; Plasma Cells; Singing
PubMed: 31072192
DOI: 10.1177/0145561319849001 -
Frontiers in Immunology 2020Due to direct contact with aquatic environment, mucosal surfaces of teleost fish are continuously exposed to a vast number of pathogens and also inhabited by high... (Review)
Review
Due to direct contact with aquatic environment, mucosal surfaces of teleost fish are continuously exposed to a vast number of pathogens and also inhabited by high densities of commensal microbiota. The B cells and immunoglobulins within the teleost mucosa-associated lymphoid tissues (MALTs) play key roles in local mucosal adaptive immune responses. So far, three Ig isotypes (i.e., IgM, IgD, and IgT/Z) have been identified from the genomic sequences of different teleost fish species. Moreover, teleost Igs have been reported to elicit mammalian-like mucosal immune response in six MALTs: gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), gill-associated lymphoid tissue (GIALT), nasal-associated lymphoid tissue (NALT), and the recently discovered buccal and pharyngeal MALTs. Critically, analogous to mammalian IgA, teleost IgT represents the most ancient Ab class specialized in mucosal immunity and plays indispensable roles in the clearance of mucosal pathogens and the maintenance of microbiota homeostasis. Given these, this review summarizes the current findings on teleost Igs, MALTs, and their immune responses to pathogenic infection, vaccination and commensal microbiota, with the purpose of facilitating future evaluation and rational design of fish vaccines.
Topics: Animals; Fish Diseases; Fish Proteins; Fishes; Gills; Host-Pathogen Interactions; Immunity, Mucosal; Immunization; Immunoglobulin D; Immunoglobulin M; Immunoglobulins; Lymphoid Tissue; Microbiota; Mucous Membrane; Organ Specificity; Peyer's Patches; Vaccination
PubMed: 33123139
DOI: 10.3389/fimmu.2020.567941 -
Frontiers in Immunology 2018Pertussis or whooping cough, mainly caused by , is a severe respiratory disease that can affect all age groups but is most severe and can be life-threatening in young... (Review)
Review
Pertussis or whooping cough, mainly caused by , is a severe respiratory disease that can affect all age groups but is most severe and can be life-threatening in young children. Vaccines against this disease are widely available since the 1950s. Despite high global vaccination coverage, the disease is not under control in any country, and its incidence is even increasing in several parts of the world. Epidemiological and experimental evidence has shown that the vaccines fail to prevent infection and transmission, although they are very effective in preventing disease. Given the high infection rate of , effective control of the disease likely requires prevention of infection and transmission in addition to protection against disease. With rare exceptions infections are restricted to the airways and do not usually disseminate beyond the respiratory epithelium. Therefore, protection at the level of the respiratory mucosa may be helpful for an improved control of pertussis. Yet, compared to systemic responses, mucosal immune responses have attracted relatively little attention in the context of pertussis vaccine development. In this review we summarize the available literature on the role of mucosal immunity in the prevention of infection. In contrast to vaccination, natural infection in humans and experimental infections in animals induce strong secretory IgA responses in the naso-pharynx and in the lungs. Several studies have shown that secretory IgA may be instrumental in the control of infection. Furthermore, studies in mouse models have revealed that infection, but not immunization with current acellular pertussis vaccines induces resident memory T cells, which may also contribute to protection against colonization by . As these resident memory T cells are long lived, vaccines that are able to induce them should provide long-lasting immunity. As of today, only one vaccine designed to induce potent mucosal immunity is in clinical development. This vaccine is a live attenuated strain delivered nasally in order to mimic the natural route of infection. Due to its ability to induce mucosal immunity it is expected that this approach will contribute to improved control of pertussis.
Topics: Animals; Bordetella pertussis; Disease Models, Animal; Humans; Immunity, Mucosal; Immunogenicity, Vaccine; Immunoglobulin A, Secretory; Mice; Pertussis Vaccine; Respiratory Mucosa; Time Factors; Treatment Outcome; Vaccination; Vaccines, Attenuated; Whooping Cough
PubMed: 30692990
DOI: 10.3389/fimmu.2018.03068 -
Trends in Immunology Apr 2018The oral mucosal barrier is constantly exposed to a plethora of triggers requiring immune control, including a diverse commensal microbiome, ongoing damage from... (Review)
Review
The oral mucosal barrier is constantly exposed to a plethora of triggers requiring immune control, including a diverse commensal microbiome, ongoing damage from mastication, and dietary and airborne antigens. However, how these tissue-specific cues participate in the training of immune responsiveness at this site is minimally understood. Moreover, the mechanisms mediating homeostatic immunity at this interface are not yet fully defined. Here we present basic aspects of the oral mucosal barrier and discuss local cues that may modulate and train local immune responsiveness. We particularly focus on the immune cell network mediating immune surveillance at a specific oral barrier, the gingiva - a constantly stimulated and dynamic environment where homeostasis is often disrupted, resulting in the common inflammatory disease periodontitis.
Topics: Animals; Host-Parasite Interactions; Humans; Immunity, Mucosal; Intestinal Mucosa; Microbiota; Mouth; Organ Specificity; Periodontitis
PubMed: 28923364
DOI: 10.1016/j.it.2017.08.005