Impaired Junctions and Invaded Macrophages in Oral Epithelia With Oral Pain

Abstract

Recurrent or chronic oral pain is a great burden for patients. Recently, the links between epithelial barrier loss and disease were extended to include initiation and propagation. To explore the effects of pathohistological changes in oral epithelia on pain, we utilized labial mucosa samples in diagnostic labial gland biopsies from patients with suspected Sjögren's syndrome (SS), because they frequently experience pain and discomfort. In most labial mucosa samples from patients diagnosed with SS, disseminated epithelial cellular edema was prevalent as ballooning degeneration. The disrupted epithelia contained larger numbers of infiltrating macrophages in patients with oral pain than in patients without pain. Immunohistochemistry revealed that edematous areas were distinct from normal areas, with disarranged cell-cell adhesion molecules (filamentous actin, E-cadherin, β-catenin). Furthermore, edematous areas were devoid of immunostaining for transient receptor potential channel vanilloid 4 (TRPV4), a key molecule in adherens junctions. In an investigation on whether impaired TRPV4 affect cell-cell adhesion, calcium stimulation induced intimate cell-cell contacts among oral epithelial cells from wild-type mice, while intercellular spaces were apparent in cells from TRPV4-knockout mice. The present findings highlight the relationship between macrophages and epithelia in oral pain processing, and identify TRPV4-mediated cell-cell contacts as a possible target for pain treatment.

SELL and IFI44 as potential biomarkers of Sjögren’s syndrome and their correlation with immune cell infiltration

“…One study found that high expression of gamma delta T cells in the peripheral blood of patients with pSS may play an auxiliary role in inducing B cells to secrete immunoglobulins and may participate in the pathological immune response of pSS (Gerli et al, 1993). Yoshimoto et al (2019) also found that most lip epithelial sections of SS patients showed cellular edema infiltrated by macrophages, which may be one of the characteristics of SS. pSS patients have elevated plasma cell levels in the peripheral blood, and the number of IgG4 + plasma cells that infiltrate the salivary glands is negatively correlated with disease characteristics; the higher the IgG4 + expression in plasma cells, the lower the positive rates of serum anti-SSA antibodies, anti-SSB antibodies, antinuclear antibodies and rheumatoid factor (Liu et al, 2017;Brokstad et al, 2018).…”

Enhanced junctional epithelial permeability in TRPV4‐deficient mice

“…As TRPV4 agonists or antagonists can regulate inflammation in pulmonary or bowel disease models, TRPV4 has been implicated as a potential target for the management of lung injury or inflammatory bowel diseases . In addition, we recently revealed an impairment of the epithelial cell‐cell contact structure with an irregular pattern of adherens junctional proteins and TRPV4 in the labial mucosal epithelium of Sjögren syndrome patients . Impaired epithelia with weaker TRPV4 expression than normal epithelia were observed together with a larger number of inflammatory cells in Sjögren syndrome patients.…”

“…36 In addition, we recently revealed an impairment of the epithelial cell-cell contact structure with an irregular pattern of adherens junctional proteins and TRPV4 in the labial mucosal epithelium of Sjögren syndrome patients. 37 Impaired epithelia with weaker TRPV4 expression than normal epithelia were observed together with a larger number of inflammatory cells in Sjögren syndrome patients. Thus, TRPV4-associated epithelial cell-cell junctions appear to play an important role in human oral mucosal epithelia.…”

Oral Mucosa as a Potential Site for Diagnosis and Treatment of Allergic and Autoimmune Diseases

“…In this regard, the study by Antunes et al [ 206 ] found that oral supplementation with capsaicin reduced macrophage infiltration and IL-33 production in proximal jejunum in a mouse model of OVA allergy. The study by Yoshimoto et al [ 207 ] explored the effects of the pathohistological changes in oral epithelia on pain by using labial mucosa samples from patients with suspected Sjogren’s syndrome (SS) because they frequently experience pain and discomfort. The disrupted epithelia contained high numbers of infiltrating macrophages and remodeled cell adhesion molecules such as filamentous actin, E-cadherin, or β-catenin.…”