Interaction of keratinocytes with infiltrating lymphocytes in allergic eczematous skin diseases

The pathology of atopic dermatitis is orchestrated on the cellular level by several different cell types in the characteristic skin lesions. In such lesions, histamine as a mediator of many biological functions is also present in high concentrations. Most of the cells involved in the inflammatory responses express the histamine H1 and H2 receptors, but drugs targeting these receptors are not clinically effective. The discovery of the fourth histamine receptor, which is differentially expressed on immune and nonimmune cells, has shed new light on the actions of histamine in the complexity of atopic dermatitis. In this review, we describe a possible genetic impact on the expression level of the histamine H4 receptor and summarize the current data regarding the activity of the histamine H4 receptor on the key effector cells in atopic dermatitis. We do so in the context of whether the histamine H4 receptor offers a novel target for effective treatments of inflammatory skin diseases.

show abstract

“…Growing evidence supports the role of KCs as enhancer cells of the inflammatory response in AD [49].…”

Section: Keratinocytesmentioning

confidence: 93%

The Role of the Histamine H4 Receptor in Atopic Dermatitis

Mommert

Gschwandtner

Gutzmer

et al. 2010

Curr Allergy Asthma Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, an in vivo assay that can accurately evaluate the effects of immune modulators/drugs on the expression level of key cytokines in targeted tissue is highly desirable for applications in medical biotechnology. Keratinocytes are known as the major source of cytokines in skin tissues [7,8], and these cells have also been shown to be the skin cell type most susceptible to gene transfection with a gene gun [9]. The purpose of this study was to establish the use of promoter activities from a panel of cytokine genes as the basis for a reporter system that can characterize the transcriptional control of cytokine gene(s) responsive to topically applied pro-or/and anti-inflammatory phytocompounds.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of phytocompounds characterized by in vivo transgenic human GM-CSF promoter activity in skin tissues

Staniforth

et al. 2008

J Biomed Sci

View full text Add to dashboard Cite

To investigate the immunomodulatory activities of phytocompounds for potential therapeutics, we devised an in vivo, transgenic, human cytokine gene promoter assay using defined epidermal skin cells as test tissue. Test compounds were topically applied to mouse skin before or after gene gun transfection, using a cytokine gene promoter-driven luciferase reporter. Croton oil, an inflammation inducer, induced transgenic GM-CSF and TNF-alpha promoter activities in skin epidermis 6-fold and 3.4-fold, respectively; however, it produced a less than 1.5-fold and 1.7-fold change in IL-1beta and IL-18 promoter activity, respectively. The phytocompound shikonin drastically inhibited inducible GM-CSF promoter activity. However, a fraction of Dioscorea batatas extract significantly increased the GM-CSF promoter activity in normal and inflamed skin. Shikonin suppressed the transcriptional activity of GM-CSF promoter by inhibiting the binding of TFIID protein complex (TBP) to TATA box. Our results demonstrate that this in vivo transgenic promoter activity assay system is cytokine gene-specific, and highly responsive to pro-inflammatory or anti-inflammatory stimuli. Currently it is difficult to profile the expression and cross-talk of various types of cytokines in vivo. This investigation has established a bona fide in vivo, in situ, immune tissue system for research into cytokine response to inflammation.

show abstract

“…E pidermal keratinocytes (KCs) are important modulators of skin inflammation through the secretion of cytokines, chemokines, arachidonic acid metabolites, and antimicrobial peptides. Depending on the circumstances, they can enhance, inhibit, and modulate T cell-dependent inflammatory diseases (1)(2)(3). For example, in the development of allergic contact dermatitis, the application of the hapten induces inflammatory signals that amplify the immune response.…”

mentioning

confidence: 99%

Cannabinoid 1 Receptors in Keratinocytes Modulate Proinflammatory Chemokine Secretion and Attenuate Contact Allergic Inflammation

Gaffal

Cron

Glodde

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Epidermal keratinocytes (KCs) and cannabinoid (CB) receptors both participate in the regulation of inflammatory responses in a mouse model for allergic contact dermatitis, the contact hypersensitivity (CHS) response to the obligate sensitizer 2,4-dinitrofluorobenzene. In this study, we investigated the cellular and molecular mechanisms how CB1 receptors attenuate CHS responses to 2,4-dinitrofluorobenzene. We used a conditional gene-targeting approach to identify the relative contribution of CB1 receptors on epidermal KCs for the control of CHS responses. To determine the underlying cellular and molecular mechanisms that regulate inflammatory responses in the effector phase of CHS, we performed further investigations on inflamed ear tissue and primary KC cultures using morphologic, molecular, and immunologic methods. Mice with a KC-specific deletion of CB1 receptors developed increased and prolonged CHS responses. These were associated with enhanced reactive epidermal acanthosis and inflammatory KC hyperproliferation in the effector phase of CHS. In vitro, primary cultures of CB1 receptor–deficient KC released increased amounts of CXCL10 and CCL8 after stimulation with IFN-γ compared with controls. In vivo, contact allergic ear tissue of CB1 receptor–deficient KCs showed enhanced expression of CXCL10 and CCL8 compared with controls. Further investigations established CCL8 as a proinflammatory chemokine regulated by CB1 receptors that promotes immune cell recruitment to allergen-challenged skin. Taken together, these results demonstrate that CB1 receptors are functionally expressed by KCs in vivo and help to limit the secretion of proinflammatory chemokines that regulate T cell–dependent inflammation in the effector phase of CHS.

show abstract

Interaction of keratinocytes with infiltrating lymphocytes in allergic eczematous skin diseases

Abstract: Keratinocytes play an active part during the acute and the chronic phase of eczema by means of cytokine production and surface molecule expression which leads to an inflammatory infiltrate in the upper layers of the skin.

Cited by 56 publications

References 47 publications

The Role of the Histamine H4 Receptor in Atopic Dermatitis

The Role of the Histamine H4 Receptor in Atopic Dermatitis

Immunomodulatory effects of phytocompounds characterized by in vivo transgenic human GM-CSF promoter activity in skin tissues

Cannabinoid 1 Receptors in Keratinocytes Modulate Proinflammatory Chemokine Secretion and Attenuate Contact Allergic Inflammation

Contact Info

Product

Resources

About