Cell-Kinetic Evidence for Increased Recruitment of Cycling Epidermal Cells in Psoriasis: The Ratio of Histone and Ki-67 Antigen Expression Is Constant

Castelijns, F.A.C.M.; Gerritsen, Marie‐Jeanne P.; Erp, P.E.J. van; Kerkhof, P.C.M. van de

doi:10.1159/000018471

Cited by 17 publications

(19 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Excessive expansion of the TA cells compartment has been recently described in psoriatic skin (77), where a defect in TA subpopulation seems to account for the epidermal abnormalities observed in the disease (78). In addition, in silico studies have simulated psoriasis by altering the TA cells (79), and psoriatic TA cells are more advanced in their life cycle than their normal counterpart (80).…”

Section: P75ntr and Epidermal Homeostasismentioning

confidence: 99%

p75 Neurotrophin Receptor in the Skin: Beyond Its Neurotrophic Function

Pincelli

2017

Front. Med.

View full text Add to dashboard Cite

p75 neurotrophin receptor (p75NTR), also known as CD271, is the low-affinity receptor that, together with the tyrosine kinase receptor tropomyosin-receptor kinase (Trk), mediate neurotrophin (NT) functions. Beside their classic role in skin innervation, NT and their receptors constitute a complex cutaneous network associated with a number of autocrine and paracrine activities. In this context, the role of p75NTR is becoming more and more important. This review will focus on the intriguing functions of p75NTR in healthy and diseased skin. First, p75NTR counterbalances the proliferative and survival activities of its cognate receptor Trk by inducing keratinocyte apoptosis. In addition, p75NTR identifies an early transit-amplifying (TA) keratinocyte population and plays a critical role in keratinocyte stem cell transition to its progeny as well as in epidermal differentiation. p75NTR is absent in psoriatic TA cells, thus rendering these cells resistant to apoptosis. On the other hand, p75NTR infection restores NT-induced apoptosis in psoriatic keratinocytes. Taken together, these results provide evidence for a critical role of p75NTR in epidermal homeostasis, while its lack may account for the TA defect in psoriasis. While the issue of p75NTR as a marker of melanoma initiating cells is still to be solved, there is strong evidence that downregulation of this receptor is a precondition to melanoma invasion and metastasis in vitro and in vivo. All in all, this review points to p75NTR as a major actor in both physiologic and pathologic conditions at the skin level.

show abstract

Section: P75ntr and Epidermal Homeostasismentioning

confidence: 99%

p75 Neurotrophin Receptor in the Skin: Beyond Its Neurotrophic Function

Pincelli

2017

Front. Med.

View full text Add to dashboard Cite

show abstract

“…In the current view, plaque psoriasis is a T-cell-mediated skin disorder, characterized by epidermal hyperproliferation and an aberrantly differentiated epidermis [1,2,3,4,5]. Activated (CD25+) memory effector (CD45RO+) T cells of the T-helper (CD4+) or the cytotoxic (CD8+) subset reside locally in lesional psoriatic skin, in both the dermis and the epidermis.…”

Section: Introductionmentioning

confidence: 99%

Identification of Lesional CD4+ CD25+ Foxp3+ Regulatory T Cells in Psoriasis

et al. 2006

View full text Add to dashboard Cite

Background: Depletion of CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (T_reg) induces autoimmune phenomena. These cells have not yet been fully characterized in the skin of psoriatic patients. Objectives: To prove that the Zenon immunofluorescent labeling technique is suitable for the demonstration of co-localization of T-cell markers and in particular to show the distribution of T_reg in psoriatic skin. Methods: In biopsies derived from normal and psoriatic skin, CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+, CD8+ CD45RO+ and CD4+ CD25+ Foxp3+ cells in the dermis and in the epidermis were immunophenotyped, using a quantitative immunofluorescent labeling technique (Zenon), analyzed and compared using image analysis. Results:The immunofluorescent labeling technique was shown to be an easy and reliable tool to demonstrate co-localization of T-cell markers. In psoriasis, all pathogenic T-cell subsets (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+ cells) were significantly increased in the dermis and in the epidermis, as compared to normal skin (all p < 0.05). Using this labeling technique we were able to reveal CD4+ CD25+ Foxp3+ T_reg in psoriatic dermis, but not in the dermis of normal skin (p < 0.0001). Conclusions:The Zenon immunofluorescence technique in combination with image analysis is suitable for the demonstration of co-localization of T-cell markers in tissue. Increased numbers of pathogenic T cells (CD4+ CD25+, CD4+ CD45RO+, CD8+ CD25+ and CD8+ CD45RO+) were shown in the dermis and epidermis, whereas CD4+ CD25+ Foxp3+ T_reg were identified in psoriatic skin with a predilection for the upper dermis.

show abstract

“…Early mathematical models describing cell renewal in psoriasis had demonstrated that the typical psoriatic tissue architecture is based not only on an increased turnover rate in the germinative cell, but also on a defect in cells transiting to the more differentiated state. More recently, Castelijns et al, 39 using kinetics parameters, have proposed that epidermal abnormalities in psoriasis are due to a defect in the transitamplifying compartment, rather than to a reduction in the cell cycle time. TA cells in psoriasis are thought to be kept in a prolonged proliferative state, which would account for an increased number of cell division, with no reduction of cell cycle time.…”

mentioning

confidence: 99%

p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes

et al. 2010

View full text Add to dashboard Cite

p75 neurotrophin receptor (p75NTR) belongs to the TNF-receptor superfamily and signals apoptosis in many cell settings. In human epidermis, p75NTR is mostly confined to the transit-amplifying (TA) sub-population of basal keratinocytes. Brainderived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4), which signals through p75NTR, induces keratinocyte apoptosis, whereas b-amyloid, a ligand for p75NTR, triggers caspase-3 activation to a greater extent in p75NTR transfected cells. Moreover, p75NTR co-immunoprecipitates with NRAGE, induces the phosphorylation of c-Jun N-terminal kinase (JNK) and reduces nuclear factor kappa B (NF-jB) DNA-binding activity. p75NTR also mediates pro-NGF-induced keratinocyte apoptosis through its co-receptor sortilin. Furthermore, BDNF or b-amyloid cause cell death in TA, but not in keratinocyte stem cells (KSCs) or in p75NTR silenced TA cells. p75NTR is absent in lesional psoriatic skin and p75NTR levels are significantly lower in psoriatic than in normal TA keratinocytes. The rate of apoptosis in psoriatic TA cells is significantly lower than in normal TA cells. BDNF or b-amyloid fail to induce apoptosis in psoriatic TA cells, and p75NTR retroviral infection restores BDNF-or b-amyloid-induced apoptosis in psoriatic keratinocytes. These results demonstrate that p75NTR has a pro-apoptotic role in keratinocytes and is involved in the maintenance of epidermal homeostasis.

show abstract

Cell-Kinetic Evidence for Increased Recruitment of Cycling Epidermal Cells in Psoriasis: The Ratio of Histone and Ki-67 Antigen Expression Is Constant

Cited by 17 publications

References 25 publications

p75 Neurotrophin Receptor in the Skin: Beyond Its Neurotrophic Function

p75 Neurotrophin Receptor in the Skin: Beyond Its Neurotrophic Function

Identification of Lesional CD4+ CD25+ Foxp3+ Regulatory T Cells in Psoriasis

p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes

Contact Info

Product

Resources

About