Abstract:The epithelial barrier of the upper respiratory tract plays a crucial role in host defense. In this study, to elucidate whether there is antigen monitoring by dendritic cells (DCs) beyond the epithelial tight-junction barrier in allergic rhinitis, we investigated the expression and function of tight junctions and characterized DCs in the epithelium of nasal mucosa from patients with allergic rhinitis. In reverse transcription-polymerase chain reaction, mRNAs of tight-junction proteins occludin, JAM-1, ZO-1, an… Show more
“…2 This dynamic regulation is important as it determines the trafficking patterns of ions, proteins and even the penetration of the dendrites of Langerhans or dendritic cells. 3,4 Not so long ago, the mere existence of epidermal TJs was debated but now the controversy is their relative importance for epidermal barrier function. For a long time, the dominant concept was that the paracellular flux of ions, water and solute in the epidermis was exclusively regulated by the intercellular lipid present within the SC (for a review see 5 ).…”
“…This is also observed in the gut and airways where DCs can establish transient TJs with the neighboring epithelial cells while penetrating the epithelial barrier to uptake antigens. 4,63 Importantly, in the gut, cldn-1 and occludin are expressed on DC cell membranes at baseline and ZO-1 expression can be rapidly induced following stimulation. 63 In the epidermis, LCs express cldn-1 64 and JAM-A 65 at baseline (Representative staining of cldn-1 and CD1a [LCs marker] in human epidermis is shown in Fig.…”
Section: Tj and Adaptive Immune Barriermentioning
confidence: 99%
“…This is supported by a recent study by Takano K. et al that noted DCs expressing cldn-1 penetrated beyond occludin-identified TJs in nasal epithelium from patients with allergic rhinitis, and this was not observed in healthy controls. 4 After LC/DC have taken up a specific antigen/allergen, they will present it to na€ ıve T cells to elicit an adaptive immune response. The character and magnitude of the adaptive T helper (Th) lymphocyte immune response (e.g., Th1, Th2, Th17, Th22, Treg) is determined by the microenvironment where the LC/DC activation occurred as well as where the na€ ıve T cells are primed (lymph nodes and possibly skin 66 ).…”
“…2 This dynamic regulation is important as it determines the trafficking patterns of ions, proteins and even the penetration of the dendrites of Langerhans or dendritic cells. 3,4 Not so long ago, the mere existence of epidermal TJs was debated but now the controversy is their relative importance for epidermal barrier function. For a long time, the dominant concept was that the paracellular flux of ions, water and solute in the epidermis was exclusively regulated by the intercellular lipid present within the SC (for a review see 5 ).…”
“…This is also observed in the gut and airways where DCs can establish transient TJs with the neighboring epithelial cells while penetrating the epithelial barrier to uptake antigens. 4,63 Importantly, in the gut, cldn-1 and occludin are expressed on DC cell membranes at baseline and ZO-1 expression can be rapidly induced following stimulation. 63 In the epidermis, LCs express cldn-1 64 and JAM-A 65 at baseline (Representative staining of cldn-1 and CD1a [LCs marker] in human epidermis is shown in Fig.…”
Section: Tj and Adaptive Immune Barriermentioning
confidence: 99%
“…This is supported by a recent study by Takano K. et al that noted DCs expressing cldn-1 penetrated beyond occludin-identified TJs in nasal epithelium from patients with allergic rhinitis, and this was not observed in healthy controls. 4 After LC/DC have taken up a specific antigen/allergen, they will present it to na€ ıve T cells to elicit an adaptive immune response. The character and magnitude of the adaptive T helper (Th) lymphocyte immune response (e.g., Th1, Th2, Th17, Th22, Treg) is determined by the microenvironment where the LC/DC activation occurred as well as where the na€ ıve T cells are primed (lymph nodes and possibly skin 66 ).…”
“…Takano et al demonstrated a different way for DCs to sample allergen without disrupting the TJs. In biopsies taken from human allergic subjects, HLA-DR+ and CD11c + DCs expressed claudin-1 and penetrated beyond occludin in the epithelium of the nasal mucosa (53). Interestingly, this process was only seen in allergic individuals, and not in healthy ones.…”
Section: Pathways Of Antigen Uptake In the Respiratory Tractmentioning
confidence: 96%
“…Studies have shown that epithelial cells stimulated with DEPs release cytokines such as IL-6, IL-8, GM-CSF, and sICAM (51). The exposure of epithelial cells from allergic subjects to DEPs and tobacco contributed to a greater constitutive and pollutant-induced release of pro-inflammatory chemokines (53). Epithelial cells may therefore play an important role in mediating the effects of air pollutants on the inflammatory response in the airways.…”
Micro‐organisms constantly invade the human body and may form a threat to our health. Traditionally, concepts of defence mechanisms have included a protective outer layer of epithelia and a vigilant immune system searching for areas where the integrity of the outer layer may be compromised. Instead of considering these elements as two independent mechanisms, we should be treating them as a single integrated system. This review will present and discuss the role of local immune‐competent cells and local epithelia in the recognition of potential pathogens and how the interaction between the two components may affect the initiation of the airway immune response. A concept emerges where airway mucosal dendritic cells act as integrators of both immunostimulatory and immunosuppressive signals that act within actively‐involved mucosal tissue.
Nasal polyposis is associated with epithelial TJP alterations. Further, the expression of TJPs in a model of inflamed respiratory mucosa is reduced in a similar fashion. Research on the histopathology of other epithelial inflammatory disorders suggests TJP alterations contribute to a self-perpetuating inflammatory state. Findings of this preliminary study support a similar process in nasal polyposis.
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