Calcitriol exerts anti‐inflammatory effects in keratinocytes treated with autoantibodies from a patient with bullous pemphigoid

Tukaj, Stefan; Grüner, D.; Tukaj, Cecylia; Zillikens, Detlef; Kasperkiewicz, Michael

doi:10.1111/jdv.12929

Cited by 19 publications

(18 citation statements)

References 19 publications

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“…Indeed, vitamin D has been shown to have an immune regulatory function and hypovitaminosis D has been correlated to an increased risk of developing autoimmune disorders (83). Moreover, vitamin D3 has been revealed to elicit down-regulation of the BP230 gene through post-transcriptional mechanisms independently by active protein synthesis (84), while non-toxic doses of calcitriol, the hormonally active vitamin D metabolite, reduced the release of the proinflammatory cytokines IL-6 and IL-8 induced by purified human BP IgG from HaCaT cells (85). A similarly beneficial effect of calcitriol has been recently reported also in mice with experimental EBA (86).…”

Section: Links Between Bullous Pemphigoid Pathogenesis and Disease-rementioning

confidence: 99%

New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update

et al. 2019

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There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.

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Section: Links Between Bullous Pemphigoid Pathogenesis and Disease-rementioning

confidence: 99%

New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update

et al. 2019

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“…Importantly, serum concentrations of 25-hydroxyvitamin D have been reported to be inversely associated with clinical disease severity in these patients, pointing toward a possible causative role of hypovitaminosis D in the disease process (Marzano et al, 2015;Moravvej et al, 2016;Zarei et al, 2014). In addition, we recently reported that calcitriol exerts antiinflammatory effects in cultured keratinocytes treated with pemphigoid autoantibodies (Tukaj et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Calcitriol Treatment Ameliorates Inflammation and Blistering in Mouse Models of Epidermolysis Bullosa Acquisita

Tukaj

Bieber

Witte

et al. 2018

Journal of Investigative Dermatology

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A link between hypovitaminosis D and development of autoimmune bullous disorders has been suggested recently, but this association has not been elaborated experimentally. Here, the role of vitamin D was investigated in epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-induced blistering skin disease. Oral administration of the hormonally active vitamin D metabolite calcitriol ameliorated clinical disease severity and dermal neutrophil infiltration in both an antibody transfer- and immunization-induced EBA mouse model. Mechanistically, calcitriol hindered immune effector cell activation as evidenced by increased L-selectin expression on Gr-1 cells in calcitriol-treated mice with antibody transfer-induced EBA, as well as suppressed in vitro immune complex-induced reactive oxygen species production in calcitriol-treated murine neutrophils. Additionally, calcitriol administration was associated with an increase of regulatory T (CD4FoxP3) and B (CD19IL10) cells as well as reduction of pro-inflammatory T helper 17 (CD4IL-17) cells in mice with immunization-induced EBA. In line, levels of circulating anti-type VII collagen autoantibodies were lower in mice that received calcitriol compared to solvent-treated animals. Together with the observed state of hypovitaminosis D in most cases of an analyzed EBA patient cohort, the results of this study support the use of vitamin D derivatives or analogs for patients with EBA and related diseases.

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“…the human keratinocytes HaCaT cells was reduced in the presence of calcitriol via inhibition of STAT3 phosphorylation and NFκB activity (Tukaj et al, 2016) (Fig. 1a).…”

Section: Experimental Therapies Using Vitamin D Analogues In the Automentioning

confidence: 94%

“…Both, 1,25(OH) 2 D and CYP11A1-derived vitamin D analogues, protect the epidermal keratinocytes against UVB-induced damage via activation of the Nrf2-dependent antioxidant response and p53-phosphorylation, as well as by induction of the DNA repair system (Chaiprasongsuk et al, 2019). In addition, both -the classical 1,25(OH) 2 D and non-calcemic CYP11A1-driven analogues, exert anti-inflammatory effects on keratinocytes by inhibiting the nuclear factor-κB (NF-κB) activity (Janjetovic et al, 2009;Tukaj et al, 2016).…”

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confidence: 99%

Vitamin D in autoimmune bullous disease

Tukaj

2020

Acta Biochim Pol

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Numerous epidemiological studies have suggested a link between vitamin D deficiency and the development of various autoimmune diseases, including diabetes mellitus type 1, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or systemic lupus erythematosus. More recently, such a link has been also proposed for autoimmune bullous diseases (AIBD). This is a relatively rare and potentially life-threatening, organ-specific group of inflammatory skin diseases characterized by the presence of tissue-bound and circulating autoantibodies against various molecules present in desmosomes (in pemphigus diseases) or hemidesmosomes (in pemphigoid diseases). In addition to the well-known role of vitamin D in calcium and phosphate homeostasis, the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol), exerts potent effects on cellular differentiation and regulation of immune responses via binding to the vitamin D receptor present in most cells of the immune system. Since cells of both, the innate and adaptive immune systems, are known to be relevant in AIBD, the role of vitamin D analogues in the treatment of patients with these disorders deserves much attention. This mini-review summarizes recent epidemiological and experimental studies on vitamin D involvement in the autoimmune bullous diseases.

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Calcitriol exerts anti‐inflammatory effects in keratinocytes treated with autoantibodies from a patient with bullous pemphigoid

Abstract: Although the results of this study are based on autoantibodies prepared from a single patient, they show that calcitriol protects from BP IgG-induced inflammatory processes in vitro, thus favouring its potential inclusion into the therapeutic repertoire of BP.

Cited by 19 publications

References 19 publications

New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update

New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update

Calcitriol Treatment Ameliorates Inflammation and Blistering in Mouse Models of Epidermolysis Bullosa Acquisita

Vitamin D in autoimmune bullous disease

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