Epithelium ; Gingiva ; immunology ; Humans ; Periodontitis ; immunology

The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system, focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.
Epithelium ; immunology ; Humans ; Immunity, Cellular ; Immunity, Mucosal ; immunology ; Mouth Diseases ; immunology ; Mouth Mucosa ; immunology ; Pharynx ; immunology ; T-Lymphocyte Subsets ; classification ; immunology

In the present work, we have examined the effect of PAF, removal of epithelium, the mechanism of desensitization, and the substances that increases the level of intracellular c-AMP on the differences of mediator release from superfused tracheal strips after passive sensitization with IgG1 versus IgE Ab. In the passive sensitized tracheal tissues, the effect of PAF and the mechanism of desensitization have been examined by PAF antagonist, CV 3988 and DFP, respectively. The epithelium was stripped from one-half of each trachea by mechanical means. Both superfused tracheal tissues were challenged with Ox-Ag. Inhibitors of mediator release were added into a superfused buffer. Hist released was determined by spectrophotofluorometer, and LT by radioimmunoassay. PAF known to mediate the allergic reaction was not released by Ag after both Ab sensitization. Epithelium removal resulted in similar contraction, Hist and LT release after IgG1 Ab activation, but in the IgE Ab activation, epithelium removal resulted in smaller contraction and Hist release. In the L-cysteine and indomethacin pretreatment after two Ab sensitization, epithelium removal decreased the release of Hist and LT. The compound 48/80 pre-challenge and epithelium removal resulted in the increase of Hist release, but in the decrease of LT release after IgG1 or IgE sensitization. The Amount of LT released by Ag after compound 48/80 pre-challenge increased in the absence or presence of epithelium after both Ab sensitization. Mediator release from tissues sensitized with both Abs was not changed by DFP. The responses of inhibitors to prevent the mediator release were more effective on the IgE Ab than on the IgG1 Ab sensitization. These studies suggest that the tracheal epithelium can act to inhibit immune- and non-immune-induced airway responses. Non-immunological responses may in part reflect the role of epithelium as a diffusion barrier and modulator of mediator release. These data also suggest that immunological responses are related to the localization and functional heterogeneity of tissue mast cells.
Animal ; Epithelium/immunology/physiology ; Female ; Guinea Pigs ; *Histamine Release ; *Immunization ; Immunoglobulin E/*immunology ; Immunoglobulin G/*immunology ; Leukotrienes/metabolism ; Mast Cells/immunology ; Support, Non-U.S. Gov't ; Trachea/*immunology/physiology

Epithelial tissues covering the external and internal surface of a body are constantly under physical, chemical or biological assaults. To protect the epithelial tissues and maintain their homeostasis, multiple layers of immune defense mechanisms are required. Besides the epithelial tissue-resident immune cells that provide the first line of defense, circulating immune cells are also recruited into the local tissues in response to challenges. Chemokines and chemokine receptors regulate tissue-specific migration, maintenance and functions of immune cells. Among them, chemokine receptor CCR10 and its ligands chemokines CCL27 and CCL28 are uniquely involved in the epithelial immunity. CCL27 is expressed predominantly in the skin by keratinocytes while CCL28 is expressed by epithelial cells of various mucosal tissues. CCR10 is expressed by various subsets of innate-like T cells that are programmed to localize to the skin during their developmental processes in the thymus. Circulating T cells might be imprinted by skin-associated antigen- presenting cells to express CCR10 for their recruitment to the skin during the local immune response. On the other hand, IgA antibody-producing B cells generated in mucosa-associated lymphoid tissues express CCR10 for their migration and maintenance at mucosal sites. Increasing evidence also found that CCR10/ligands are involved in regulation of other immune cells in epithelial immunity and are frequently exploited by epithelium-localizing or -originated cancer cells for their survival, proliferation and evasion from immune surveillance. Herein, we review current knowledge on roles of CCR10/ligands in regulation of epithelial immunity and diseases and speculate on related important questions worth further investigation.
B-Lymphocytes ; cytology ; immunology ; Cell Lineage ; Cell Movement ; genetics ; immunology ; Chemokine CCL27 ; genetics ; immunology ; Chemokines, CC ; genetics ; immunology ; Epithelial Cells ; cytology ; immunology ; Epithelium ; immunology ; Gene Expression Regulation ; immunology ; Humans ; Immunity, Mucosal ; Immunoglobulin A ; biosynthesis ; immunology ; Mucous Membrane ; cytology ; immunology ; Receptors, CCR10 ; genetics ; immunology ; Signal Transduction ; genetics ; immunology ; T-Lymphocytes ; cytology ; immunology

Airway remodeling in asthma is a result of persistent inflammation and epithelial damage in response to repetitive injury. Recent studies have identified several important mediators associated with airway remodeling in asthma, including transforming growth factor-beta, interleukin (IL)-5, basic fibroblast growth factor, vascular endothelial growth factor, LIGHT, tumor necrosis factor (TNF)-alpha, thymic stromal lymphopoietin, IL-33, and IL-25. In addition, the epithelium mesenchymal transformation (EMT) induced by environmental factors may play an important role in initiating this process. Diagnostic methods using sputum and blood biomarkers as well as radiological interventions have been developed to distinguish between asthma sub-phenotypes. Human clinical trials have been conducted to evaluate biological therapies that target individual inflammatory cells or mediators including anti IgE, anti IL-5, and anti TNF-alpha. Furthermore, new drugs such as c-kit/platelet-derived growth factor receptor kinase inhibitors, endothelin-1 receptor antagonists, calcium channel inhibitors, and HMG-CoA reductase inhibitors have been developed to treat asthma-related symptoms. In addition to targeting specific inflammatory cells or mediators, preventing the initiation of EMT may be important for targeted treatment. Interestingly, bronchial thermoplasty reduces smooth muscle mass in patients with severe asthma and improves asthma-specific quality of life, particularly by reducing severe exacerbation and healthcare use. A wide range of different therapeutic approaches has been developed to address the immunological processes of asthma and to treat this complex chronic illness. An important future direction may be to investigate the role of mediators involved in the development of airway remodeling to enhance asthma therapy.
Airway Resistance/*immunology ; Asthma/immunology/*pathology/therapy ; Biological Therapy ; Cytokines ; Eosinophils ; Epithelium ; Humans ; Inflammation/immunology/*pathology/therapy ; Interleukin-5 ; Tumor Necrosis Factor-alpha

The cell surface molecule identified by a monoclonal antibody(TE-1) to human thymic epithelial cell showed the specificity for thymic epithelial cells of both the cortex and medulla. TE-1 reacted with the epithelial cells of normal thymus and thymoma in fresh frozen tissues. The antigen recognized by TE-1 was mostly confined to the cell surface membrane and arranged in reticular network with long processes between thymocytes. On immunohistochemical analysis, TE-1 did not recognize normal epithelial cells of the uterine cervix, skin and stomach, and neoplastic cells of squamous cell carcinoma and gastric adenocarcinoma, all of which were stained with anti-cytokeratin monoclonal antibody. Among the tumor cell lines tested with flow cytometry, most of epithelial and all of hematopoietic cell origin were not labeled with TE-1. In summary, TE-1 appears to be a monoclonal antibody against a surface antigen of human thymic epithelial cell that is immunohistologically different from known epithelial cell surface antigens reported so far.
Animals ; Antibodies, Monoclonal/biosynthesis/*immunology ; Antibody Specificity ; Antigens, Surface/*immunology ; Epithelium/immunology ; Fluorescent Antibody Technique ; Humans ; Immunoenzyme Techniques ; Immunoglobulin G/immunology ; Immunoglobulin Isotypes/immunology ; Mice ; Mice, Inbred BALB C ; Neoplasms/immunology ; Thymoma/immunology ; Thymus Gland/*immunology ; Thymus Neoplasms/immunology ; Tumor Cells, Cultured

This study was undertaken to localize fibronectin and type IV collagen in the cultured retinal pigment epithelial cell by means of immunofluorescent staining and immunocytochemical methods. Immunofluorescent staining and immunocytochemical methods revealed fibronectin and type IV collagen localized on the extracellular membrane of the cultured retinal pigment epithelial cell. Ultrastructural immunocytochemical technique also revealed fibronectin associated with extracellular tissue. This study demonstrated that fibronectin and type IV collagen are an integral component of the extracellular matrix of the human retinal pigment epithelial cell in vitro.
Cells, Cultured ; Collagen/*analysis ; Extracellular Matrix/*analysis/immunology ; Fibronectins/*analysis ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Pigment Epithelium of Eye/*analysis

The regulated transport of salt and water is essential to the integrated function of many organ systems, including the respiratory, reproductive, and digestive tracts. Airway epithelial fluid secretion is a passive process that is driven by osmotic forces, which are generated by ion transport. The main determinant of a luminally-directed osmotic gradient is the mucosal transport of chloride ions (Cl(-)) into the lumen. As with many epithelial cells, a number of classic signal transduction cascades are involved in the regulation of ion transport. There are two well-known intracellular signaling systems: an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) and an increase in the rate of synthesis of cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP). Therefore, Cl(-) secretion is primarily activated via the opening of apical Ca(2+)- or cAMP-dependent Cl(-) channels at the apical membrane. The opening of basolateral Ca(2+)- or cAMP-activated K(+) channels, which hyperpolarizes the cell to maintain the driving force for Cl(-) exit through apical Cl(-) channels that are constitutively open, is also important in regulating transepithelial ion transport. P2Y receptors are expressed in the apical and/or basolateral membranes of virtually all polarized epithelia to control the transport of fluid and electrolytes. Human airway epithelial cells express multiple nucleotide receptors. Extracellular nucleotides, such as UTP and ATP, are calcium-mobilizing secretagogues. They are released into the extracellular space from airway epithelial cells and act on the same cell in an autocrine fashion to stimulate transepithelial ion transport. In addition, recent data support the role of P2Y receptors in releasing inflammatory cytokines in the bronchial epithelium and other immune cells.
Biological Transport ; Cell Membrane ; physiology ; Chloride Channels ; physiology ; Cyclic AMP ; physiology ; Cytokines ; immunology ; Epithelial Cells ; physiology ; Epithelium ; immunology ; physiology ; Humans ; Ion Transport ; Receptors, Purinergic P2Y ; immunology ; physiology ; Signal Transduction

OBJECTIVETo study the mechanism of promoting wound healing with mixed grafting of autologous and allogeneic microskin in rats.

METHODSFifteen male Wistar rats served as alloskin donor. Forty-five female SD rats with full-thickness skin defect served as recipients in the study. In part one experiment, 27 SD rats were randomly divided into group I (n = 9, without allogeneic microskin), group II (n = 9, with mixed grafting of allogeneic microskin at area expansion rate of 10:1); group III (n = 9, with mixed grafting of allogeneic microskin at area expansion rate of 10:3) with grafting with the same amount of autologous microskin at area expansion rate of 10:1. In part two experiment, 18 SD rats were also divided into group I (n = 6, with autologous microskin only); group II (n = 6, with mixed grafting of autologous and allogeneic microskin with area expansion rate of 20:1 and 20:3 respectively); group III (n = 6, with mixed grafting of autologous and allogeneic microskin with area expansion rate of 20:1 and 20:6, respectively). Biopsy samples were obtained from healed wound area of SD rats in each group at different time points after operation. The histological changes, epidermal thickness, and immunohistochemical staining of Integrin beta1 were observed.

RESULTS(1) HE staining showed the thickness of epidermis in each group increased obviously, and various amounts of mononuclear cell infiltration and different degrees of vasodilation appeared in the dermal layer during 2 - 4 weeks. (2) Epidermal thickness in group II and III of part one experiment were significantly thicker than that in group I during 2 - 4 weeks after operation (P < 0.05), and the similar result was also seen in part two experiment on 3 and 4 weeks after operation (P < 0.05). (3) A positive staining pattern for Integrin beta1 was seen in the suprabasal layers (especially in the spinous and granular layers) in all groups. In part one experiment, the expression of Integrin beta1 in group II and III were obviously higher than that in group I on 2 week after operation (P < 0.01), and the expression of Integrin beta1 in group II (10 982 +/- 2169) was also higher than that in group III (4240 +/- 512, P < 0.01); the expression of Integrin beta1 in group II was still higher than that in group I and III (P < 0.01) 3 and 4 weeks after operation. In part two experiment, the expression of Integrin beta1 in group III (1618 +/- 171) was higher than that in group I 3 weeks after operation (1060 +/- 146, P < 0.05).

CONCLUSIONThe ectopic and increased expression of Integrin beta1 was closely associated with the proliferation and differentiation of epidermal cells, wound reepithelialization and thickened epidermis in mixed grafting of autologous and allogeneic microskin. Integrin beta1 may be responsible in promoting wound healing.

Animals ; Epidermis ; metabolism ; Epithelium ; metabolism ; Female ; Integrin beta1 ; immunology ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Skin Transplantation ; Transplantation, Homologous ; Wound Healing

BACKGROUNDCornea epithelial cells play early and crucial roles in the initiation of ocular surface responses to pathogens. Participation of toll-like receptor (TLR) 2 and TLR4, which are major forms of fungi receptors, may be involved in Aspergillus fumigatus induced immune responses. The objective of the present study was to examine whether inactive Aspergillus fumigatus conidia induce NF-kappaB activation and production of proinflammatory cytokines, and whether the expression of TLR2 and TLR4 were amplified by conidia in cultured immortalized human corneal epithelial cells (THCEs). This may contribute to our knowledge of the mechanism by which the host cornea can successfully defend against invasive fungi.

METHODSAspergillus fumigatus conidia were used to challenge THCE cells. THCE cells were harvested after 0.5, 1, 2 or 4 hours incubation. Real-time quantitative PCR was performed to determine the expression of TLR2, TLR4, TNF-alpha and IL-8. Western blotting was performed to determine the expression of NF-kappaB. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression of TNF-alpha and IL-8. And the release of TNF-alpha and IL-8 in the cell supernatant were also assessed by ELISA with or without pretreatment with TLR2 and TLR4 neutralizing antibodies.

RESULTSAspergillus fumigatus conidia elicited the expression of TLR2, TLR4, TNF-alpha and IL-8 mRNA in THCEs. Exposure of THCE cells to Aspergillus fumigatus conidia resulted in NF-kappaB activation, which increased at 30 minutes (increased from 11.35+/-2.74 in the controls to 19.12+/-3.48, P<0.05) and thereafter increased steadily up to 4 hours after challenge (P<0.01). Concomitant with NF-kappaB activation, secretion of TNF-alpha and IL-8 in conidia-challenged cells was increased in a time-dependent manner. Incubation of THCE cells with TLR2 antibody or TLR4 antibody before conidia challenge resulted in inhibition of conidia-induced TNF-alpha and IL-8 secretion (P<0.05), TLR2 antibody and TLR4 antibody together significantly increased inhibition of the conidia-induced secretion of TNF-alpha and IL-8 from THCE cells (P<0.01).

CONCLUSIONAspergillus fumigatus conidia stimulates THCEs inflammatory response through a pathway dependent on TLR2 and TLR4 signaling.

Aspergillus fumigatus ; immunology ; Cells, Cultured ; Epithelium, Corneal ; cytology ; immunology ; Humans ; Interleukin-8 ; biosynthesis ; NF-kappa B ; metabolism ; Toll-Like Receptor 2 ; physiology ; Toll-Like Receptor 4 ; physiology ; Tumor Necrosis Factor-alpha ; biosynthesis