I am delving into the intricate interplay between oral microbiota and the immune system, specifically in the context of autoimmune diseases affecting the oral cavity. I am keen on understanding the nuanced immunopathogenic mechanisms at play. Are there recent breakthroughs or emerging perspectives in the field that shed light on the molecular dynamics between oral microbiome dysbiosis and the initiation or progression of autoimmune conditions such as oral lichen planus or pemphigus vulgaris?
Hello Zarmina Ehtesham
Oral lichen planus
Oral lichen planus (OLP) is a chronic autoimmune, T cell-mediated inflammatory disease of the oral mucosa. When infection occurs in the oral cavity, OLP-mediating antigens recruit T cells to the target oral mucosa, where they direct an immune response that culminates in keratinocyte cell death and long-term disease.
Oral keratinocytes release a multitude of proinflammatory cytokines, including TNF-α, IL-1β, G-CSF, IL-12, and IL-6, to recruit T cells. Activated APCs including dendritic cells (DCs), macrophages, mast cells, and activated oral keratinocytes activate T cells, produce the primary OLP immune response in which cytotoxic CD8+ T cells drive keratinocyte apoptosis through the release of cytotoxins and CD4+ Th1 T lymphocytes maintain a pro-inflammatory state.
Moreover, mast cells produce chymases, which damage the epithelial basement membrane directly or indirectly through the activation of MMP-9. Some other Th subsets are involved in the development of OLP. Th17 cells secrete elevated levels of IL-17 and IL-23, while Th9 cells secrete IL-9 and IL-17 in OLP lesions, where these cells are thought to play key roles in oral immunity. Some evidence indicates that the proportion of peripheral Th17 cells and pro-inflammatory cytokine IL-17 levels are significantly elevated in patients with OLP. Pro-inflammatory cytokine IL-17 increases the proportion of functionally impaired CD4+CD25+ regulatory T cells in OLP patients, ultimately leading to OLP.
The pathogenesis of OLP includes antigen-specific and non-specific mechanisms. Antigen-specific mechanisms involve T-cell activation following antigen presentation and apoptosis of oral keratinocytes. The non-specific mechanisms consist of the overproduction of CCL2, the activation of MMP-9, and mast cell degranulation. Thus, a complex immune cell relationship exists during the process of OLP.
For more information you may want to refer to the article attached below.
https://www.frontiersin.org/articles/10.3389/fmicb.2022.1009018/full
Pemphigus vulgaris
Pemphigus is an autoimmune, mucocutaneous disease in which circulating autoantibodies (IgG) are directed against a protein, desmoglein3 (DSG3) in the desmosomal complex, causing the disruption of intercellular junctions and the loss of cell-to-cell adhesion. However, there is evidence also suggesting that pemphigus blistering is not solely caused by autoantibody targeting to DSG3 but rather results from intracellular signaling mediated by non-DSGs targeting autoantibodies that leads to shrinkage of cell and apoptosis. For more information you may want to refer to the article attached below.
Article Evolving Mechanisms in the Pathophysiology of Pemphigus Vulg...
Other articles that may help are provided below.
https://www.tandfonline.com/doi/full/10.3109/15419061.2014.943397
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00136/full
Article How does acantholysis occur in Pemphigus vulgaris: A critical review
Article Are desmoglein autoantibodies essential for the immunopathog...
Article The oral microbiome in autoimmune diseases: friend or foe?
Best.
Hi Zarmina,
The list of articles and answer by Malcolm Nobre are quite comprehensive. I would like to suggest these two reviews on OLP:
The human microbiome in immunobullous disorders and lichen planus.
https://academic.oup.com/ced/article/47/3/522/6693219?login=true#no-access-message#no-access-message
The immunopathogenesis of oral lichen planus-Is there a role for mucosal associated invariant T cells?
Article The Immunopathogenesis of Oral Lichen Planus - is there a ro...
Kind regards
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