T cell–mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis

Trautmann, Axel; Akdiş, Mübeccel; Kleemann, Daniela; Altznauer, Frank; Simon, Hans‐Uwe; Graeve, T.; Noll, Michaela; Bröcker, Eva‐B.; Blaser, Kurt; Akdiş, Cezmi A.

doi:10.1172/jci9199

Cited by 430 publications

(387 citation statements)

References 65 publications

(67 reference statements)

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“…It was found that although mice lacking both pathways were able to generate hapten-specific CD8 π T lymphocytes, they were unable to mount CHS reactions (34). Similar conclusions regarding the importance of Fas-induced cell death in the pathogenesis of allergic contact dermatitis and other cutaneous inflammatory reactions derived from studies of human skin (35). It is important to acknowledge, however, that cells other than CD8 π Tc1-type lymphocytes have the ability to induce cytotoxicity.…”

Section: Effector Cell Cytotoxic Functionmentioning

confidence: 79%

Allergic contact dermatitis: the cellular effectors

2002

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Contact hypersensitivity reactions are mediated by lymphocytic effector cells. Until recently it was believed that the most important of these were CD4 π T lymphocytes. However, there is growing evidence that in many instances the predominant effector cell may be a CD8 π T lymphocyte, with in some instances CD4 π cells performing a counter-regulatory function. Here we review the roles of CD4 π T helper (Th) cells and CD8 π T cytotoxic (Tc) cells, and their main functional subpopulations (respectively, Th1 and Th2 cells and Tc1 and Tc2 cells) in the elicitation of contact hypersensitivity reactions and consider the implications of effector cell selectivity for the biology of allergic contact dermatitis.

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Section: Effector Cell Cytotoxic Functionmentioning

confidence: 79%

Allergic contact dermatitis: the cellular effectors

2002

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“…In our previous studies, IFN-␥ and sFas-ligand were identified as keratinocyte apoptosis-inducing factors within the activated T cell supernatants. The type of T cell-induced keratinocyte death was also shown to be apoptosis by using several different apoptosis-specific methods (23,25).…”

Section: Ifn-␥- Tnf-␣- and T Cell-mediated Death Of Human Keratinocmentioning

confidence: 99%

“…Apoptosis of keratinocytes induced by T cells and mediated by IFN-␥ and Fas (CD95) is a crucial event in the transition from activation of the immune system to the manifestation of eczematous dermatitis (23). Apparently, keratinocyte apoptosis is an activation-induced cell death, because IFN-␥ up-regulates Fas, ICAM-1, and HLA-DR and renders keratinocytes susceptible to apoptosis (24).…”

mentioning

confidence: 99%

A Second Step of Chemotaxis After Transendothelial Migration: Keratinocytes Undergoing Apoptosis Release IFN-γ-Inducible Protein 10, Monokine Induced by IFN-γ, and IFN-γ-Inducible α-Chemoattractant for T Cell Chemotaxis Toward Epidermis in Atopic Dermatitis

Klunker¹,

Trautmann²,

Akdiş³

et al. 2003

The Journal of Immunology

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109

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Activation and skin-selective homing of T cells and their effector functions in the skin represent sequential immunological events in the pathogenesis of atopic dermatitis (AD). Apoptosis of keratinocytes, induced mainly by T cells and mediated by IFN-γ and Fas, is the essential pathogenetic event in eczema formation. Keratinocyte apoptosis appears as activation-induced cell death in AD. By IFN-γ stimulation, chemokines such as IFN-γ-inducible protein 10, monokine induced by IFN-γ, and IFN-γ-inducible α-chemoattractant are strongly up-regulated in keratinocytes. These chemokines attract T cells bearing the specific receptor CXCR3, which is highly expressed on T cells isolated from skin biopsies of AD patients. Accordingly, an increased T cell chemotaxis was observed toward IFN-γ-treated keratinocytes. Supporting these findings, enhanced IFN-γ-inducible protein 10, monokine induced by IFN-γ, and IFN-γ-inducible α-chemoattractant expression was observed in lesional AD skin by immunohistochemical staining. These results indicate a second step of chemotaxis inside the skin after transendothelial migration of the inflammatory cells. Keratinocytes undergoing apoptosis in acute eczematous lesions release chemokines that attract more T cells toward the epidermis, which may further augment the inflammation and keratinocyte apoptosis.

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“…Elevated IFN-g mRNA levels are noted in lesions of cutaneous LE (234). This cytokine has recently been shown to be pivotal in the induction of keratinocyte apoptosis in two skin inflammatory conditions: allergic contact dermatitis and atopic dermatitis (235). In these conditions, T cell derived IFNg promotes keratinocyte apoptosis by enhancing their expression of Fas (235).…”

Section: Uva Mediated Cytokine Expressionmentioning

confidence: 99%