TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2

Pasparakis, Manolis; Courtois, Gilles; Hafner, Martin; Schmidt-Supprian, Marc; Nenci, Arianna; Toksoy, Atiye; Krampert, Monika; Goebeler, Matthias; Gillitzer, R.; Israël, Alain; Krieg, Thomas; Rajewsky, Klaus; Haase, Ingo

doi:10.1038/nature00820

Cited by 440 publications

(478 citation statements)

References 29 publications

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“…IKKb deficiency in the skin decreases the proliferation rate of isolated primary keratinocytes and impairs NF-kB activation in response to TNF or IL-1b. 50 However, skin-specific deletion of IKKb does not affect epidermal differentiation as such, nor does it lead to premature apoptosis during keratinocyte cornification, but rather disrupts immune homeostasis in the skin. 50 Mutations in the human X-linked gene encoding NEMO/IKKg are linked to the male-lethal skin disease incontinentia pigmenti.…”

Section: Nf-jbmentioning

confidence: 99%

“…50 However, skin-specific deletion of IKKb does not affect epidermal differentiation as such, nor does it lead to premature apoptosis during keratinocyte cornification, but rather disrupts immune homeostasis in the skin. 50 Mutations in the human X-linked gene encoding NEMO/IKKg are linked to the male-lethal skin disease incontinentia pigmenti. 51 Affected female neonates develop blisters and, paradoxically, an inflammatory response in the epidermis.…”

Section: Nf-jbmentioning

confidence: 99%

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Death penalty for keratinocytes: apoptosis versus cornification

et al. 2005

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Homeostasis implies a balance between cell growth and cell death. This balance is essential for the development and maintenance of multicellular organisms. Homeostasis is controlled by several mechanisms including apoptosis, a process by which cells condemned to death are completely eliminated. However, in some cases, total destruction and removal of dead cells is not desirable, as when they fulfil a specific function such as formation of the skin barrier provided by corneocytes, also known as terminally differentiated keratinocytes. In this case, programmed cell death results in accumulation of functional cell corpses. Previously, this process has been associated with apoptotic cell death. In this overview, we discuss differences and similarities in the molecular regulation of epidermal programmed cell death and apoptosis. We conclude that despite earlier confusion, apoptosis and cornification occur through distinct molecular pathways, and that possibly antiapoptotic mechanisms are implicated in the terminal differentiation of keratinocytes.

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Section: Nf-jbmentioning

confidence: 99%

Section: Nf-jbmentioning

confidence: 99%

Death penalty for keratinocytes: apoptosis versus cornification

et al. 2005

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“…Moreover, antigenic stimulation of BCR also activates IKK complex and results in nuclear localization of transcription factor NF-jB [8, 15,16]. Protein kinase C-b (PKC-b) is shown to connect BCR signaling to IKK activation upon BCR stimulation [17].…”

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confidence: 99%

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Pappu¹,

Lin²

2006

Eur J Immunol

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NF‐κB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen‐mediated activation of B cells. CARD domain and MAGUK‐domain containing protein‐1 (CARMA1), recently identified adaptor molecule, has been shown to play an essential role in BCR‐induced NF‐κB activation. CARMA1‐deficient B cells fail to proliferate upon BCR stimulation, leading to defective humoral responses. Surprisingly, CARMA1‐deficient B cells are also defective in CD40‐induced proliferation. The mechanisms responsible for CD40‐induced proliferation defect have not yet been characterized. In this study, we show that signaling cascades activated by CD40 stimulation are largely unaffected in CARMA1‐deficient B cells. Instead, we have found that the defective proliferation of CARMA1‐deficient B cells is due to two events. First, CARMA1‐deficient B cells show defective cell‐cycle progression. Secondly, the numbers of marginal zone (MZ) B cells, which are the main responders upon CD40 stimulation, are greatly diminished in CARMA1‐deficient mice. Since B cell maturation requires basal signaling through BCR and NF‐κB activation, we propose that impaired BCR signaling in CARMA1‐deficient mice leads to defective maturation of MZ B cell population, which in turn, contributes to impaired proliferation upon CD40 stimulation.

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“…A disruption of this status quo results in changes in proliferation and apoptosis as a result of immunologic cross-talk. 21,22 A likely explanation for this controversy may lie in the complexity of the pathway, the different models used, or cross-talk with other major signaling axes such as TP53 and mitogen-activated protein kinase. 23 One emerging aspect, which largely was ignored until recently, is the involvement of scaffold proteins that provide a link between membrane receptors and the IKK complex.…”

mentioning

confidence: 99%