Manolis Pasparakis

Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappa B signals (2009)

Derudder, Emmanuel, Cadera, Emily J., Val, J. Christoph, Wang, Jing, Fox, Casey J., Zha, Shan, ...

By genetically ablating I kappa B kinase (IKK)-mediated activation of the transcription factor NF-kappa B in the B cell lineage and by analyzing a mouse mutant in which immunoglobulin...

Epithelial NEMO links innate immunity to chronic intestinal inflammation (2007)

Nenci, Arianna, Becker, Christoph, Wullaert, Andy, Gareus, Ralph, Van Loo, Geert, Danese, Silvio, ...

Deregulation of intestinal immune responses seems to have a principal function in the pathogenesis of inflammatory bowel disease(1-4). The gut epithelium is critically involved in the maintenance of...

Skin lesion development in a mouse model of incontinentia pigmenti is triggered by NEMO deficiency in epidermal keratinocytes and requires TNF signaling (2006)

Nenci, Arianna, Huth, Marion, Funteh, Alfred, Schmidt-Supprian, Marc, Bloch, Wilhelm, Metzger, Daniel, ...

NF-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase, is essential for NF-κB activation. Mutations disrupting the X-linked NEMO gene cause incontinentia pigmenti (IP), a...

Skin lesion development in a mouse model of incontinentia pigmenti is triggered by NEMO-deficiency in epidermal keratinocytes and requires TNF signaling (2006)

Nenci, Arianna, Huth, Marion, Funteh, Alfred, Schmidt-Supprian, Marc, Bloch, Wilhelm, Metzger, Daniel, ...

NF-κB Essential Modulator (NEMO), the regulatory subunit of the IκB kinase, is essential for NF-κB activation. Mutations disrupting the X-linked NEMO gene cause incontinentia pigmenti (IP), a...

Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury (2005)

Assmus, Ulrike, Wüstefeld, Torsten, Meyer Zu Vilsendorf, Andreas, Schmidt-Supprian, Mark, ...

The inhibitor of NF-kappaB (I-kappaB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-kappaB essential modulator (NEMO), and is involved in the activation of NF-kappaB by various...

Peyer’s patch organogenesis is intact yet formation of B lymphocyte follicles is defective in peripheral lymphoid organs of mice deficient for tumor necrosis factor and its 55-kDa receptor

Pasparakis, Manolis, Alexopoulou, Lena, Grell, Matthias, Pfizenmaier, Klaus, Bluethmann, Horst, Kollias, George

Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin (LT) ligand and receptor system has recently revealed essential roles for these molecules in lymphoid tissue development...

Tumor Necrosis Factor Alpha-Deficient, but Not Interleukin-6-Deficient, Mice Resist Peripheral Infection with Scrapie

Mabbott, Neil A., Williams, Alun, Farquhar, Christine F., Pasparakis, Manolis, Kollias, Giorgos, Bruce, Moira E.

In most peripheral infections of rodents and sheep with scrapie, infectivity is found first in lymphoid tissues and later in the central nervous system (CNS). Cells within the germinal centers (GCs)...

Inhibition of NF-κB activation in macrophages increases atherosclerosis in LDL receptor–deficient mice

Kanters, Edwin, Pasparakis, Manolis, Gijbels, Marion J.J., Vergouwe, Monique N., Partouns-Hendriks, Iris, Fijneman, Remond J.A., ...

Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor NF-κB is a key regulator of inflammation, immune responses, cell survival, and cell...

Conditional disruption of IκB kinase 2 fails to prevent obesity-induced insulin resistance

Röhl, Mathias, Pasparakis, Manolis, Baudler, Stephanie, Baumgartl, Julia, Gautam, Dinesh, Huth, Marion, ...

The inhibitor of NF-κB (IκB) kinases (IKK1[α] and IKK2[β]), the catalytic subunits of the IKK complex, phosphorylate IκB proteins on serine residues, targeting them for degradation and thus...

Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-κB activation

Schmidt-Supprian, Marc, Tian, Jane, Grant, Ethan P., Pasparakis, Manolis, Maehr, René, Ovaa, Huib, ...

Natural killer-like (NK) T, regulatory T (TR), and memory type T cells display surface phenotypes reminiscent of activated T cells. Previously, we reported that the generation of TR cells and, to a...

Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury

Luedde, Tom, Assmus, Ulrike, Wüstefeld, Torsten, Meyer Zu Vilsendorf, Andreas, Roskams, Tania, Schmidt-Supprian, Mark, ...

The inhibitor of NF-κB (I-κB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-κB essential modulator (NEMO), and is involved in the activation of NF-κB by various stimuli. IKK2 or...

Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation

Stratis, Athanasios, Pasparakis, Manolis, Rupec, Rudolf A., Markur, Doreen, Hartmann, Karin, Scharffetter-Kochanek, Karin, ...

Psoriasis is a common skin disease, the pathogenesis of which has not yet been resolved. In mice, epidermis-specific deletion of inhibitor of NF-κB (IκB) kinase 2 (IKK2) results in a skin phenotype...

Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration

Mourkioti, Foteini, Kratsios, Paschalis, Luedde, Tom, Song, Yao-Hua, Delafontaine, Patrick, Adami, Raffaella, ...

NF-κB is a major pleiotropic transcription factor modulating immune, inflammatory, cell survival, and proliferative responses, yet the relevance of NF-κB signaling in muscle physiology and disease...

Peyer’s patch organogenesis is intact yet formation of B lymphocyte follicles is defective in peripheral lymphoid organs of mice deficient for tumor necrosis factor and its 55-kDa receptor

Pasparakis, Manolis, Alexopoulou, Lena, Grell, Matthias, Pfizenmaier, Klaus, Bluethmann, Horst, Kollias, George

Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin (LT) ligand and receptor system has recently revealed essential roles for these molecules in lymphoid tissue development...

Tumor Necrosis Factor Alpha-Deficient, but Not Interleukin-6-Deficient, Mice Resist Peripheral Infection with Scrapie

Mabbott, Neil A., Williams, Alun, Farquhar, Christine F., Pasparakis, Manolis, Kollias, Giorgos, Bruce, Moira E.

In most peripheral infections of rodents and sheep with scrapie, infectivity is found first in lymphoid tissues and later in the central nervous system (CNS). Cells within the germinal centers (GCs)...

Inhibition of NF-κB activation in macrophages increases atherosclerosis in LDL receptor–deficient mice

Kanters, Edwin, Pasparakis, Manolis, Gijbels, Marion J.J., Vergouwe, Monique N., Partouns-Hendriks, Iris, Fijneman, Remond J.A., ...

Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor NF-κB is a key regulator of inflammation, immune responses, cell survival, and cell...

Conditional disruption of IκB kinase 2 fails to prevent obesity-induced insulin resistance

Röhl, Mathias, Pasparakis, Manolis, Baudler, Stephanie, Baumgartl, Julia, Gautam, Dinesh, Huth, Marion, ...

The inhibitor of NF-κB (IκB) kinases (IKK1[α] and IKK2[β]), the catalytic subunits of the IKK complex, phosphorylate IκB proteins on serine residues, targeting them for degradation and thus...

Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-κB activation

Schmidt-Supprian, Marc, Tian, Jane, Grant, Ethan P., Pasparakis, Manolis, Maehr, René, Ovaa, Huib, ...

Natural killer-like (NK) T, regulatory T (TR), and memory type T cells display surface phenotypes reminiscent of activated T cells. Previously, we reported that the generation of TR cells and, to a...

Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury

Luedde, Tom, Assmus, Ulrike, Wüstefeld, Torsten, Meyer Zu Vilsendorf, Andreas, Roskams, Tania, Schmidt-Supprian, Mark, ...

The inhibitor of NF-κB (I-κB) kinase (IKK) complex consists of 3 subunits, IKK1, IKK2, and NF-κB essential modulator (NEMO), and is involved in the activation of NF-κB by various stimuli. IKK2 or...

Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation

Stratis, Athanasios, Pasparakis, Manolis, Rupec, Rudolf A., Markur, Doreen, Hartmann, Karin, Scharffetter-Kochanek, Karin, ...

Psoriasis is a common skin disease, the pathogenesis of which has not yet been resolved. In mice, epidermis-specific deletion of inhibitor of NF-κB (IκB) kinase 2 (IKK2) results in a skin phenotype...

Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration

Mourkioti, Foteini, Kratsios, Paschalis, Luedde, Tom, Song, Yao-Hua, Delafontaine, Patrick, Adami, Raffaella, ...

NF-κB is a major pleiotropic transcription factor modulating immune, inflammatory, cell survival, and proliferative responses, yet the relevance of NF-κB signaling in muscle physiology and disease...

Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration

Mourkioti, Foteini, Kratsios, Paschalis, Luedde, Tom, Song, Yao-Hua, Delafontaine, Patrick, Adami, Raffaella, ...

Oligodendrocyte Apoptosis and Primary Demyelination Induced by Local TNF/p55TNF Receptor Signaling in the Central Nervous System of Transgenic Mice : Models for Multiple Sclerosis with Primary Oligodendrogliopathy

Akassoglou, Katerina, Bauer, Jan, Kassiotis, George, Pasparakis, Manolis, Lassmann, Hans, Kollias, George, ...

The scientific dogma that multiple sclerosis (MS) is a disease caused by a single pathogenic mechanism has been challenged recently by the heterogeneity observed in MS lesions and the realization...

M17, a gene specific for germinal center (GC) B cells and a prognostic marker for GC B-cell lymphomas, is dispensable for the GC reaction in mice

Schenten, Dominik, Egert, Angela, Pasparakis, Manolis, Rajewsky, Klaus

In T-cell–dependent antibody responses, antigen-specific B cells undergo a phase of secondary antibody diversification in germinal centers (GCs). Somatic hypermutation (SHM) introduces mutations...

Tumor Necrosis Factor (TNF) Receptor Shedding Controls Thresholds of Innate Immune Activation That Balance Opposing TNF Functions in Infectious and Inflammatory Diseases

Xanthoulea, Sofia, Pasparakis, Manolis, Kousteni, Stavroula, Brakebusch, Cord, Wallach, David, Bauer, Jan, ...

Tumor necrosis factor (TNF) is a potent cytokine exerting critical functions in the activation and regulation of immune and inflammatory responses. Due to its pleiotropic activities, the amplitude...

IκB Kinase Signaling Is Essential for Maintenance of Mature B Cells

Pasparakis, Manolis, Schmidt-Supprian, Marc, Rajewsky, Klaus

Nuclear factor (NF)-κB proteins play crucial roles in immune responses and cellular survival. Activation of NF-κB is mediated by the IκB kinase (IKK) complex, which is composed of two kinases,...

Complementation of Lymphotoxin α Knockout Mice with Tumor Necrosis Factor–expressing Transgenes Rectifies Defective Splenic Structure and Function

Alexopoulou, Lena, Pasparakis, Manolis, Kollias, George

Lymphotoxin (LT)α knockout mice, as well as double LTα/tumor necrosis factor (TNF) knockout mice, show a severe splenic disorganization with nonsegregating T/B cell zones and complete absence of...

Hepatic NF-κB essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis

Wunderlich, F. Thomas, Luedde, Tom, Singer, Stephan, Schmidt-Supprian, Marc, Baumgartl, Julia, Schirmacher, Peter, ...

Development of obesity-associated insulin resistance and diabetes mellitus type 2 has been linked to activation of proinflammatory pathways in the liver, leading to impaired insulin signal...

IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver

Luedde, Tom, Heinrichsdorff, Jan, De Lorenzi, Rossana, De Vos, Rita, Roskams, Tania, Pasparakis, Manolis

Inflammatory destruction of intrahepatic bile ducts is a common cause of vanishing bile duct syndrome and cholestasis, often progressing to biliary cirrhosis and liver failure. However, the molecular...

BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells

Otipoby, Kevin L., Sasaki, Yoshiteru, Schmidt-Supprian, Marc, Patke, Alina, Gareus, Ralph, Pasparakis, Manolis, ...

B cell activating factor (BAFF) signals through BAFF-R to promote mature B cell survival. Recent analyses of BAFF-induced signaling revealed direct association between augmented B cell metabolic...

Defective Osteoclastogenesis by IKKβ-null Precursors Is a Result of Receptor Activator of NF-κB Ligand (RANKL)-induced JNK-dependent Apoptosis and Impaired Differentiation*

Otero, Jesse E., Dai, Simon, Foglia, Domenica, Alhawagri, Muhammad, Vacher, Jean, Pasparakis, Manolis, ...

It has been reported previously that inhibitory κB kinase (IKK) supports osteoclastogenesis through NF-κB-mediated prevention of apoptosis. This finding suggests that the ligand for receptor...

Sustained Oscillations of NF-κB Produce Distinct Genome Scanning and Gene Expression Profiles

Sung, Myong-Hee, Salvatore, Luigi, De Lorenzi, Rossana, Indrawan, Anindya, Pasparakis, Manolis, Hager, Gordon L., ...

NF-κB is a prototypic stress-responsive transcription factor that acts within a complex regulatory network. The signaling dynamics of endogenous NF-κB in single cells remain poorly understood. To...

p38α MAPK inhibits JNK activation and collaborates with IκB kinase 2 to prevent endotoxin-induced liver failure

Heinrichsdorff, Jan, Luedde, Tom, Perdiguero, Eusebio, Nebreda, Angel R, Pasparakis, Manolis

Activation of c-Jun amino-terminal kinase (JNK) facilitates tumour necrosis factor (TNF)-induced cell death. The p38 mitogen-activated protein kinase pathway is induced by TNF stimulation, but it has...