Human keratinocytes constitutively express IL‐4 receptor molecules and respond to IL‐4 with an increase in B7/BB1 expression

Junghans, Volker; Jung, Thomas; Neumann, Christine

doi:10.1111/j.1600-0625.1996.tb00135.x

Cited by 33 publications

(22 citation statements)

References 45 publications

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“…This effect of IL-4 in keratinocytes is in agreement with the fact that human keratinocytes constitutively express IL-4 receptor and that its expression is increased in some epidermal proliferative diseases such as psoriasis [48,49]. Moreover, it is known that infiltrating activated T-cells are present at the dermal-epidermal junction, and that the infiltration precedes the development of epidermal hyperproliferation [55].…”

Section: Discussionsupporting

confidence: 76%

“…Since 3␤-HSD type 1 is expressed in the skin [3,9], and human keratinocytes constitutively express the IL-4 receptor [48,49], the effect of IL-4 on type 1 3␤-HSD expression was preliminary investigated in HaCaT human immortalized keratinocytes [10]. This effect was further characterized in the present study.…”

Section: The Hacat Cells Also Possess Estrogenic 17␤-hsd Activity As mentioning

confidence: 97%

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Characterization and modulation of sex steroid metabolizing activity in normal human keratinocytes in primary culture and HaCaT cells

Gingras

Turgeon

Brochu

et al. 2003

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionsupporting

confidence: 76%

Section: The Hacat Cells Also Possess Estrogenic 17␤-hsd Activity As mentioning

confidence: 97%

Characterization and modulation of sex steroid metabolizing activity in normal human keratinocytes in primary culture and HaCaT cells

Gingras

Turgeon

Brochu

et al. 2003

The Journal of Steroid Biochemistry and Molecular Biology

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“…Therefore, the effects of IL-4 and IL-13 on epidermal morphologic features and gene expression are the result of interactions of IL-4 and IL-13 with the keratinocytes, which express receptors for IL-4 and IL-13. 27,28 The combination of IL-4 and IL-13 induced increased intraepidermal intercellular edema, a clinical hallmark of acute and subacute eczema. A recent study suggested that induction of spongiosis by the cytokines IL-4, IL-13, and IFN-␥ was mediated by decreased E-cadherin expression and simultaneously increased hyaluronan production by keratinocytes, 29 resulting in osmotic movement of water into the intercellular compartment of the epidermis.…”

Section: Discussionmentioning

confidence: 99%

Type 2 Helper T-Cell Cytokines Induce Morphologic and Molecular Characteristics of Atopic Dermatitis in Human Skin Equivalent

Kamsteeg

Bergers

Boer

et al. 2011

The American Journal of Pathology

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Both the immune system and the epidermis likely have an important role in the pathogenesis of atopic dermatitis (AD). The objective of the present study was to develop a human skin equivalent model exhibiting morphologic and molecular characteristics of AD in a controlled manner. Skin equivalents generated from normal adult human keratinocytes were stimulated with type 2 T-helper cell (Th2) cytokines IL-4 and IL-13, and morphologic features and gene expression of the epidermis were studied. Th2 cytokines induced intercellular edema similar to spongiotic changes observed in lesional AD as assessed at histopathologic analysis and electron microscopy. Furthermore, genes known to be specifically expressed in epidermis of patients with AD such as CAII and NELL2 were induced. In contrast, expression of psoriasis-associated genes such as elafin and hBD2 was not changed. Th2 cytokines caused DNA fragmentation in the keratinocytes, which could be inhibited by the caspase inhibitor Z-VAD, which suggests that apoptosis was induced. In addition, up-regulation of the death receptor Fas was observed in keratinocytes after Th2 cytokine stimulation. IL-4 and IL-13 induced phosphorylation of the signaling molecule STAT6. It was concluded that the skin equivalent model described herein may be useful in investigation of the epidermal aspects of AD and for study of drugs that act at the level of keratinocyte biology.

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“…They also express similar Toll-like receptors to those produced by professional APCs (45). Keratinocytes express various ␥c-dependent cytokine receptors, respond to ␥c-dependent cytokines, and express Jak3, suggesting that the ␥c/Jak3 signaling pathway may be important in keratinocyte function (2,29,43,57). As with cells of the myeloid lineage, keratinocytes are not reconstituted following BMT.…”

Section: Discussionmentioning

confidence: 99%

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

Goldschmidt¹,

Kennedy

et al. 2006

J Virol

115

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Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (␥c) gene and is identical clinically and immunologically to human XSCID, making it a true homologue of the human disease. Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitute normal T-cell function but, in contrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstitute normal humoral immune function. Shortly after our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous infections containing a newly described canine papillomavirus. This is analogous to the late-onset cutaneous papillomavirus infection recently described for human XSCID patients following BMT. Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% developed chronic canine papillomavirus infection. Six of the transplanted dogs that developed cutaneous papillomas were maintained for >3 1/2 years post-BMT for use as breeders. Four of these six dogs (67%) developed invasive squamous cell carcinoma (SCC), with three of the dogs (75%) eventually developing metastatic SCC, an extremely rare consequence of SCC in the dog. This finding raises the question of whether SCC will develop in transplanted human XSCID patients later in life. Canine XSCID therefore provides an ideal animal model with which to study the role of the ␥c-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC.Severe combined immunodeficiency (SCID) is a heterogeneous group of diseases characterized by the inability to mount humoral and cell-mediated immune responses, and it is invariably fatal within the first 2 years of life (9, 46). X-linked SCID (XSCID) is the most common form of the disease, representing approximately 50% of all human SCID cases (9, 18). XSCID is caused by mutations in the common gamma (␥c) subunit of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 (reviewed in references 4 and 34). Thus, the XSCID phenotype is the complex result of multiple cytokine defects. The shared usage of the ␥c subunit by receptors for growth factors that are critical for normal B-, NK-, and T-cell development and function explains the profound immunologic abnormalities and clinical severity of the disease.Since the first successful HLA-identical bone marrow transplant in a boy with SCID in 1968 (19), bone marrow transplantation (BMT) has become the treatment of choice for all forms of SCID (10,18,22). SCID patients receiving a histocompatible (HLA-identical) BMT have Ͼ90% long-term survival rates (10,18,22). However, the majority of patients do not have a histocompatible donor. Haploidentical (half-matched) BMT with T-cell depletion to prevent fatal graft-versus-host disease has become the standard therapy for SCID patients who lack a histocompatible donor (10,18,22). Although T-cell depletion...

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Human keratinocytes constitutively express IL‐4 receptor molecules and respond to IL‐4 with an increase in B7/BB1 expression

Cited by 33 publications

References 45 publications

Characterization and modulation of sex steroid metabolizing activity in normal human keratinocytes in primary culture and HaCaT cells

Characterization and modulation of sex steroid metabolizing activity in normal human keratinocytes in primary culture and HaCaT cells

Type 2 Helper T-Cell Cytokines Induce Morphologic and Molecular Characteristics of Atopic Dermatitis in Human Skin Equivalent

Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

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