T-Cell-Mediated Injury to Keratinocytes: Insights from Animal Models of the Lichenoid Tissue Reaction

Dutz, Jan P.

doi:10.1038/jid.2008.242

Cited by 18 publications

(12 citation statements)

References 52 publications

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“…First, LS has been associated with several inflammatory disorders, including LP, psoriasis, vitiligo, and morphea , with evidence suggesting that pDCs play a significant role in the underlying pathogenesis . Second, it has recently become evident that activation of the type I IFN system is involved in many skin diseases characterized by the interface dermatitis pattern . The predominant source of type I IFNs in these disorders appears to be pDCs, which have been shown to play a major role in LE, LP, and dermatomyositis ().…”

Section: Discussionmentioning

confidence: 99%

Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus

Badr

Abadi

Kurban

et al. 2016

Pediatric Dermatology

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Background and aims Vd2 T cells have predominantly been investigated in tumour immuno-surveillance and the host defense against viral invasion. The precise role of Vd2 T cells in the pathogenesis of SLE remains elusive. Methods We measured the proportion of peripheral Vd2 T cells as well as the status and chemokine receptor expression profiles in SLE patients and healthy control (HC). In addition, Vd2 T cell infiltration in the kidneys of patients with lupus nephritis was examined. Results The percentage of peripheral Vd2 T cells in new-onset SLE was decreased, and negatively correlated with the SLE Disease Activity Index score and the severity of proteinuria. These cells had a decreased apoptosis but an increased proliferation , and they showed increased accumulation in SLE kidneys. Moreover, IL-21 production and CD40L, CCR4, CCR7, CCR8, CXCR1 and CX3CR1 expression in Vd2 T cells from SLE patients was significantly higher than from HC (p<0.05), and these factors were down-regulated in association with the repopulation of peripheral Vd2 T cells in patients who were in remission (p<0. Background and aims Systemic Lupus Erythematosus (SLE) is associated with an increased IFN gene signature detectable in the peripheral blood. Plasmacytoid dendritic cells (pDC) are potent producers of IFNa in response to TLR9 and TLR7-agonists. pDCs which express high levels of CD123 (IL-3Ra) can be depleted by JNJ-56022473 (JNJ-473), a novel Fc-engineered neutralising and depleting therapeutic antibody targeting CD123. Methods We investigated the effects of pDC depletion with JNJ-473 on IFNa production and gene expression within SLE patient PBMC (n=8) stimulated with TLR-agonists, SLE-immune complexes (IC, SLE IgG with necrotic cell lysates (NCL)) and sera from SLE patients with NCL. Results Stimulation with CpGc, SLE-IC or SLE sera was able to induce high levels of IFNa, which was greatly decreased by pDC depletion with JNJ-473. SLE-IC and SLE sera stimulation also induced the differential expression of hundreds of genes and could induce similar genes to TLR9-agonism. pDC depletion with JNJ-473 prevented the upregulation of TLR9-induced genes. JNJ-473 conferred minimal effects on the induction of genes in response to the TLR4-agonist LPS. Furthermore , a distinct 11-gene IFN signature was induced by CpGc and SLE-IC that was significantly reduced by treatment with JNJ-473, suggesting that the depletion of pDCs with JNJ-473 could have distinct and specific effects on the detectable IFN signature in many SLE patients. Conclusions Depletion of pDCs with JNJ-473 is able to dramatically decrease IFNa production and IFN gene signature induced by TLR9-agonists and SLE-IC. Background and aims Glucocorticoid-induced Leucine Zipper (GILZ) is a GC-inducible gene with multiple immune-regulatory functions, and GILZ deficiency in mice results in the development of a lupus-like phenotype. In Systemic Lupus Erythematosus (SLE), plasmacytoid dendritic cells (pDCs) are major producers of Type 1 interferons (IFN) in response to nucleic acid-containin...

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Section: Discussionmentioning

confidence: 99%

Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus

Badr

Abadi

Kurban

et al. 2016

Pediatric Dermatology

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“…LP is a cutaneous immune‐mediated disease characterized by a type‐1 cytokine pattern. T cell‐mediated injury of basal keratinocytes has been considered as the major pathogenetic step of the disease 22 . Interferon‐γ and TNF‐α play a crucial role in the amplification of skin inflammation, by inducing adhesion molecules on keratinocytes and by releasing chemotactic factors through resident cells.…”

Section: Discussionmentioning

confidence: 99%

Off‐label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study

Klein¹,

Coras²,

Landthaler³

et al. 2011

Acad Dermatol Venereol

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“…The presence of juxta‐epithelial band of lymphocytes is a pathognomonic feature of OLP. Chemokines secreted by activated epithelial cells facilitate recruitment of lymphocytes to the mucosa [5,6]. Oral epithelial cells are activated by exogenous/endogenous stimuli via TLRs [9].…”

Section: Discussionmentioning

confidence: 99%

Soluble forms of Toll-like receptor 4 are present in human saliva and modulate tumour necrosis factor-α secretion by macrophage-like cells

Zunt¹,

Burton

Goldblatt³

et al. 2009

Clinical and Experimental Immunology

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SummaryIn health, mucosal inflammation is prevented by tightly regulated responses via Toll-like receptors (TLR) that interact with specific microbe associated molecular patterns. Currently, 13 TLRs have been identified. Based on the specificity of ligand recognition, TLR-2 and TLR-4 can recognize most oral commensal microorganisms. Recent identification of some soluble TLRs (sTLRs) suggests additional regulatory roles for these receptors. We report here the presence of sTLR-4 polypeptides in adult human saliva. Functionally, the salivary sTLR-4 suppressed cytokine secretion by activated macrophages. The sTLR-4 levels were elevated significantly in oral lichen planus (OLP), a chronic inflammatory condition of the oral mucosa characterized by clinical persistence. In contrast, the epithelial cells in the saliva of OLP subjects expressed significantly reduced TLR-2 and TLR-4 mRNA that correlated with fewer bacteria/salivary epithelial cells. Investigating the soluble and cellular components of saliva is useful in identifying potential biomarkers for oral mucosal lesions.

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T-Cell-Mediated Injury to Keratinocytes: Insights from Animal Models of the Lichenoid Tissue Reaction

Cited by 18 publications

References 52 publications

Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus

Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus

Off‐label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study

Soluble forms of Toll-like receptor 4 are present in human saliva and modulate tumour necrosis factor-α secretion by macrophage-like cells

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