Keratinocytes constitutively express the CD95 ligand molecule on the plasma membrane: an in situ immunoelectron microscopy study on ultracryosections of normal human skin

Panfilis, G. De; Semenza, Diego; Llombart‐Bosch, Antonio; Mulder, Aat A.; Mommaas, A. Mieke; Pasolini, G.

doi:10.1046/j.1365-2133.2002.04746.x

Cited by 9 publications

(6 citation statements)

References 43 publications

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“…No granules were apparently seen on the surface of the occasionally observed melanocytes. On the other hand, keratinocytes showed a scarce labeling even in these resting conditions on the plasma membrane, as already reported (40). Finally, we had not, unfortunately, the opportunity to observe dermal dendritic cells in our specimens.…”

Section: Resultssupporting

confidence: 87%

The tolerogenic molecule CD95‐L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.

Panfilis

Venturini

Llombart‐Bosch³

et al. 2003

Experimental Dermatology

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Although dendritic cells (DC) are well known for their immunogenic capacities, they may even induce peripheral T-cell tolerance, and such a tolerogenic potential can be exerted in mouse through the expression on the DC plasma membrane of the CD95-ligand (CD95-L) molecule, which is able to trigger apoptosis of CD95-expressing antigen-specific T cells. We therefore asked whether epidermal DC, namely Langerhans' cells (LC), either resting (i.e. within the epidermis, 'in situ') or activated (i.e. suspended from the epidermis) or both, could express the CD95-L molecule on the plasma membrane. For such a purpose, two colloidal gold-immunoelectron microscopy (IEM) double-step procedures were carried out: an 'in situ' method, able to investigate resting LC, was performed on ultrathin frozen sections obtained by ultracryomicrotomy (UCMT) of normal skin biopsies; a pre-embedding (P-E) method, able to investigate suspended LC, was performed on epidermal cells (EC) suspended from normal skin specimens. In UCMT/IEM sections, resting LC showed gold particles within the cytoplasm but very rarely within organelles and never along the plasma membrane: resting LC are therefore capable of synthesizing CD95-L but not of expressing it in a functional location, thus autoreactive phenomena against CD95-expressing EC being avoided in normal epidermis. On the other hand, in P-E/IEM preparations, suspended LC showed several gold particles along the plasma membrane: activated LC are therefore capable of expressing CD95-L in a functional location, thus bearing the potential to exert tolerogenic capabilities against CD95-expressing T cells, e.g. to prevent inflammatory/autoimmune cutaneous disorders and/or favor the resolution thereof.

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Section: Resultssupporting

confidence: 87%

The tolerogenic molecule CD95‐L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.

Panfilis

Venturini

Llombart‐Bosch³

et al. 2003

Experimental Dermatology

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“…Although both of them coexist on keratinocytes, DR4 seems to be more effective [32]. These receptors do not take part in terminal differentiation of keratinocytes [33]. There are also TRAIL receptors on keratinocytes which do not promote apoptosis, because recombinant TRAIL does not induce apoptosis on healthy keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

The Expression of Selected Proapoptotic Molecules in Dermatitis Herpetiformis

Zebrowska

Erkiert‐Polguj

Wągrowska-Danilewicz

et al. 2012

Clinical and Developmental Immunology

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The role of the process of apoptosis is investigated in the pathogenesis of many autoimmune diseases; however at present, there is not much information about its role in dermatitis herpetiformis. Skin biopsies were taken from 18 DH patients and from 10 healthy subjects. The localization and expression of Bax, Fas, FasL, TRAIL, TRAIL-R in skin lesions, and perilesional skin were studied by immunohistochemistry. Expression of Bax, Fas, and Fas ligand was detected in the keratinocytes in skin biopsies from DH patients. Expression of TRAIL and TRAIL receptor was confirmed in epidermis, infiltration cells, and some fibroblasts. The expression of examined molecules in biopsies from healthy people was observed only in single cells. There were statistically significant differences between lesional, perilesional, and healthy skin of control group in Bax expression analysis and between lesional skin and control group in Fas, FasL, and TRAIL expression. There were statistically significant differences between control group and perilesional skin in Bax and FasL expression. Our results show that selected proapoptotic molecules may take part in pathogenesis of dermatitis herpetiformis, but the role of apoptosis in this process is not clear.

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“…HaCaT cells were maintained in the culture for a maximum of 20 passages. Primary adult human epidermal keratinocytes and cell culture reagents were purchased from ScienCell Laboratory (Carlsbad, CA) and were cultured according to their protocol (de Panfilis et al, 2002;Eckert et al, 2002;Song et al, 2002).…”

Section: Cell Linesmentioning

confidence: 99%

Enhanced Glycogen Metabolism Supports the Survival and Proliferation of HPV-Infected Keratinocytes in Condylomata Acuminata

Zhang

Guo

et al. 2020

Journal of Investigative Dermatology

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Condylomata acuminata (CA) is caused by human papillomavirus (HPV) infections of keratinocytes and is a common sexually transmitted disease. The main clinical feature and risk of CA is the high recurrence of genital warts formed by infected keratinocytes. Metabolic reprogramming of most types of mammalian cells including keratinocytes can provide energy and intermediates essential for their survival. Here, we report that HPV infection develops a hypoxic microenvironment in CA warts by inducing the accumulation of glycogen and increased glycogen metabolism in the infected keratinocytes in a hypoxia-inducible factor 1a (HIF-1a) -dependent pathway. Our in vitro studies show that the increased glycogen metabolism is essential for the survival and proliferation of keratinocytes. Regarding its mechanism of action, glycogenolysis generates glucose-1-phosphate that fluxes into the pentose phosphate pathway and, then, generates abundant nicotinamide adenine dinucleotide phosphate, thereby ensuring high levels of glutathione in keratinocytes under hypoxia. The abrogation of glycogen synthesis and glycogenolysis decreases the ratio of glutathione and glutathione disulfide and increases the level of ROS, further resulting in the impairment of keratinocyte survival. Collectively, our work offers an insight into the metabolic reprogramming in the development of CA and implies that the intervention of glycogen metabolism would be a promising therapeutic target for CA.

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Keratinocytes constitutively express the CD95 ligand molecule on the plasma membrane: an in situ immunoelectron microscopy study on ultracryosections of normal human skin

Cited by 9 publications

References 43 publications

The tolerogenic molecule CD95‐L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.

The tolerogenic molecule CD95‐L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.

The Expression of Selected Proapoptotic Molecules in Dermatitis Herpetiformis

Enhanced Glycogen Metabolism Supports the Survival and Proliferation of HPV-Infected Keratinocytes in Condylomata Acuminata

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