New mechanisms of skin innate immunity: ASK1-mediated keratinocyte differentiation regulates the expression of beta-defensins, LL37, and TLR2.

Abstract:

:Epidermal keratinocytes differentiate and form a multilayered epidermis, which is the primary barrier between the body and the outer environment. As the epidermis is constantly exposed to a variety of microbial pathogens, its function of resisting microbial pathogens is vital. This characteristic feature is formed during differentiation. Immunohistochemical analysis revealed that the upper epidermis of normal human skin expresses beta-defensins 1-3 and LL37. We hypothesized that epidermal keratinocytes develop an innate immune barrier based on human beta-defensins (hBD) and LL37 during differentiation. To prove this, we introduced an active form of the apoptosis signal-regulating kinase-1 (ASK1), an intracellular regulator of keratinocyte differentiation, into cultured normal human keratinocytes. Transfection of this active form, ASK1-DeltaN, significantly enhanced the expression of hBD1-3 and LL37. In addition, a p38 inhibitor abolished this induction, indicating that the ASK1-p38 cascade regulates the expression of hBD1-3 and LL37. Furthermore, the ASK1-p38 pathway also regulated the expression of Toll-like receptor (TLR)2 in keratinocytes. Contact between S. aureus and keratinocytes resulted in the phosphorylation of p38 and induced the expression of hBD2 and hBD3. Moreover, the p38 inhibitor reduced this induction. In conclusion, the ASK1-p38 cascade regulates the innate immunity of the skin by forming an immune barrier consisting of hBD, LL37, and TLR2 during epidermal differentiation.

journal_name

Eur J Immunol

authors

Sayama K,Komatsuzawa H,Yamasaki K,Shirakata Y,Hanakawa Y,Ouhara K,Tokumaru S,Dai X,Tohyama M,Ten Dijke P,Sugai M,Ichijo H,Hashimoto K

doi

10.1002/eji.200425827

keywords:

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

1886-95

issue

6

eissn

0014-2980

issn

1521-4141

journal_volume

35

pub_type

杂志文章
  • Immature B cells from human and mouse bone marrow can change their surface light chain expression.

    abstract::The capacity of bone marrow-derived surface immunoglobulin-positive (sIg+) human and mouse immature B cells, generated either in vitro or in vivo, to change their light (L) chain expression, has been assayed by the number of cells which change in vitro from one type of L chain to the other type, or to no sIg at all. I...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830251118

    authors: Ghia P,Gratwohl A,Signer E,Winkler TH,Melchers F,Rolink AG

    更新日期:1995-11-01 00:00:00

  • Suppressive and pro-inflammatory roles for IL-4 in the pathogenesis of experimental drug-induced liver injury.

    abstract::The pathogenesis of immune-mediated drug-induced liver injury (DILI) following halogenated anesthetics, carbamazepine or alcohol has not been fully elucidated. Detecting cytochrome P450 2E1 (CYP2E1) IgG4 auto-antibodies in anesthetic DILI patients suggests a role for IL-4 in this hapten-mediated process. We investigat...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200838135

    authors: Njoku DB,Li Z,Washington ND,Mellerson JL,Talor MV,Sharma R,Rose NR

    更新日期:2009-06-01 00:00:00

  • xid mice fail to express an anti-dextran immune response but carry alpha(1-3)dextran-specific lymphocytes in their potential repertoire.

    abstract::Even after repeated immunizations with alpha(1-3)dextran (Dex) male (CBA/N x BALB/c)F1 mice fail to produce specific antibodies whereas nondefective female littermates express an idiotype-positive anti-Dex immune response. This failure of xid mice to express serum anti-Dex immunoglobulins is not only limited to immuni...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830181111

    authors: Selinka HC,Bösing-Schneider R

    更新日期:1988-11-01 00:00:00

  • A quantitative assay of peptide-dependent class I assembly.

    abstract::We have developed a quantitative assay for the measurement of class I assembly induced by peptide. We have applied this assay to H-2Db, Kb and HLA-A2.1 with a panel of 49 overlapping peptides derived from HIV-1 gag protein. We find that the effects of peptide on assembly form a continuous distribution. By defining pos...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830210909

    authors: Elvin J,Cerundolo V,Elliott T,Townsend A

    更新日期:1991-09-01 00:00:00

  • The effects of a monoclonal antibody to interferon-gamma on experimental autoimmune thyroiditis (EAT): prevention of disease and decrease of EAT-specific T cells.

    abstract::CBA/J mice immunized with thyroglobulin (Tg) develop an experimental autoimmune thyroiditis (EAT) with lymphocytic infiltration of the thyroid glands, autoantibodies to Tg and occurrence of EAT-specific T cells. When these mice were treated for 4 weeks after immunization with 1 mg/week of a monoclonal antibody (mAb) t...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830230143

    authors: Tang H,Mignon-Godefroy K,Meroni PL,Garotta G,Charreire J,Nicoletti F

    更新日期:1993-01-01 00:00:00

  • Transgenic expression of an immunologically privileged retinal antigen extraocularly enhances self tolerance and abrogates susceptibility to autoimmune uveitis.

    abstract::Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU). The nature and extent of tolerance to immunologically privileged self antigens is poorly understood. To investigate whether transgenic expression of IRBP extraocula...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200001)30:1<272::AID-IMMU272>3.0

    authors: Xu H,Wawrousek EF,Redmond TM,Nickerson JM,Wiggert B,Chan CC,Caspi RR

    更新日期:2000-01-01 00:00:00

  • Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: implications for vaccination of immunocompromised individuals.

    abstract::Studies based on either MHC class II-knockout or CD4+ T cell-depleted murine models have demonstrated a critical role for CD4+ T cells in the generation of CD8+ T cell memory. However, it is difficult to extend these findings to immunocompromised humans where a complete loss of CD4+ T cells is rarely observed. Here, w...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200737933

    authors: Smith C,Martinez M,Cooper L,Rist M,Zhong J,Khanna R

    更新日期:2008-07-01 00:00:00

  • Local checkpoint inhibition of CTLA-4 as a monotherapy or in combination with anti-PD1 prevents the growth of murine bladder cancer.

    abstract::Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in metastatic cancer patients. However, patients treated with CTLA-4 blockade have suffered from immune-related adverse events, most likely due to the breadth of the induced T-cell activation. Here, we investigated the efficacy of a local low-dose...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201646583

    authors: van Hooren L,Sandin LC,Moskalev I,Ellmark P,Dimberg A,Black P,Tötterman TH,Mangsbo SM

    更新日期:2017-02-01 00:00:00

  • T cell clones interacting with accessory and T helper cells for a proliferative response.

    abstract::The requirement for cell interactions in T cell activation has been studied with two continuously in vitro growing T cell clones. These clones are specific for minor histocompatibility antigens, are H-2K restricted, and one clone is functionally a cytolytic T lymphocyte. Both can proliferate when interleukin 2 is adde...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830141011

    authors: Di Pauli R,Brückner T

    更新日期:1984-10-01 00:00:00

  • The T cell receptor beta genes of Xenopus.

    abstract::cDNA of the T cell receptor beta (TCRB) have been isolated from the anuran amphibian Xenopus and they show strong structural homology to TCRB sequences of other vertebrates. Ten BV families, two D segments, ten J segments, and a single C region have been defined so far. Each V family consists of one to two members per...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830270327

    authors: Chretien I,Marcuz A,Fellah J,Charlemagne J,Du Pasquier L

    更新日期:1997-03-01 00:00:00

  • Signaling through human killer cell activating receptors triggers tyrosine phosphorylation of an associated protein complex.

    abstract::Our understanding of the biology of human natural killer (NK) cells has significantly advanced in recent years upon identification of a family of NK cell-expressed genes that encode killer cell inhibitory receptors (KIR). Individual KIR can selectively bind various HLA class I allotypes and consequently transduce inhi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199802)28:02<599::AID-IMMU

    authors: Campbell KS,Cella M,Carretero M,López-Botet M,Colonna M

    更新日期:1998-02-01 00:00:00

  • Soluble anti-mu monoclonal antibodies prime resting B cells to secrete immunoglobulins in response to interleukins-4 and -5.

    abstract::Soluble anti-immunoglobulin (Ig) antibodies have been generally found to inhibit Ig secretion in B cells, via largely unknown mechanisms. To investigate this phenomenon further a two-step culture system was used in which B cells are primed for 24-72 h with various soluble monoclonal or polyclonal anti-Ig antibodies: a...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830220629

    authors: Phillips C,Klaus GG

    更新日期:1992-06-01 00:00:00

  • Identity of PB76 differentiation antigen and lymphocyte alkaline phosphatase.

    abstract::Alkaline phosphatases (APases, EC 3.1.3.1) are ecto-enzymes bound to cell membranes by a phosphatidyl-inositol anchor. We have previously shown that APase is present on activated murine B cells and its expression correlates with the process of B cell differentiation into immunoglobulin secretion. Recently, a monoclona...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830200436

    authors: Márquez C,De la Hera A,Leonardo E,Pezzi L,Strasser A,Martínez-A C

    更新日期:1990-04-01 00:00:00

  • Antibody response to phosphorylcholine in vitro. II. Analysis of T-dependent and T-independent responses.

    abstract::Spleen cells from BALB/c mice primed with keyhole limpet hemocyanin (KLH), were stimulated with heat-killed vaccine of rough Pneumococcus pneumoniae R36A (Pn) and/or phosphorylcholine (PC)-coupled KLH to induce an anti-PC response in vitro. The response to PC-KLH was found to be T-dependent while it is T-independent t...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830060605

    authors: Quintáns J,Cosenza H

    更新日期:1976-06-01 00:00:00

  • Involvement of the CD4 molecule in a post-activation event on T cell proliferation.

    abstract::A monoclonal antibody (mAb) directed to a human leukocyte 55-kDa cell surface molecule with identical cellular distribution and biochemical properties to the CD4 was able to inhibit T cell proliferation induced either in a mixed lymphocyte culture or by activation with mAb anti-CD3, anti-CD2 or phytohemagglutinin. The...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830170205

    authors: Carrera AC,Sanchez-Madrid F,Lopez-Botet M,Bernabeu C,De Landazuri MO

    更新日期:1987-02-01 00:00:00

  • Experimental autoimmune thyroiditis (EAT) in mice lacking the IFN-gamma receptor gene.

    abstract::To investigate the role of interferon-gamma (IFN-gamma) in experimental autoimmune thyroidits (EAT), H-2k mice with a disrupted IFN-gamma receptor (IFN-gamma R) gene were immunized with porcine thyroglobulin (pTg). We observed that EAT occurred on day 19 and remitted on day 35 in IFN-gamma R-deficient (IFN-gamma R(0/0...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199801)28:01<201::AID-IMMU

    authors: Alimi E,Huang S,Brazillet MP,Charreire J

    更新日期:1998-01-01 00:00:00

  • CXCR4 antagonist AMD3100 redistributes leukocytes from primary immune organs to secondary immune organs, lung, and blood in mice.

    abstract::AMD3100 (plerixafor), is a specific CXCR4 antagonist approved by the FDA for mobilizing hematopoietic stem cells from bone marrow to blood for transplantation in cancer. AMD3100 also mobilizes most mature leukocyte subsets to blood; however, their source and trafficking potential have not been fully delineated. Here, ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201445245

    authors: Liu Q,Li Z,Gao JL,Wan W,Ganesan S,McDermott DH,Murphy PM

    更新日期:2015-06-01 00:00:00

  • Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors.

    abstract::Since signals via CD40 and the B cell receptor are known to synergize to induce B cell activation, we have analyzed the pocket protein/E2F complexes in mouse B lymphocytes following stimulation by anti-IgM, anti-CD40, alone or together. We find that E2F4 and DP1 form the predominant E2F heterodimers in the G0 and G1 p...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199910)29:10<3380::AID-IMM

    authors: Lam EW,Glassford J,van der Sman J,Banerji L,Pizzey AR,Shaun N,Thomas B,Klaus GG

    更新日期:1999-10-01 00:00:00

  • A catch-22: Interleukin-22 and cancer.

    abstract::Barrier surfaces of multicellular organisms are in constant contact with the environment and infractions to the integrity of epithelial surfaces is likely a frequent event. Interestingly, components of the immune system, that can be activated by environmental compounds such as the microbiota or nutrients, are interspe...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审

    doi:10.1002/eji.201747183

    authors: Hernandez P,Gronke K,Diefenbach A

    更新日期:2018-01-01 00:00:00

  • MARCO, an innate activation marker of macrophages, is a class A scavenger receptor for Neisseria meningitidis.

    abstract::The scavenger receptor-A I/II (SR-A) and macrophage receptor with collagenous domain (MARCO) share a common domain organisation and ligand repertoire, including selected polyanions and gram-positive and -negative organisms, but differ in fine specificity of ligand binding, tissue distribution and regulation. Neisseria...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200535389

    authors: Mukhopadhyay S,Chen Y,Sankala M,Peiser L,Pikkarainen T,Kraal G,Tryggvason K,Gordon S

    更新日期:2006-04-01 00:00:00

  • A natural protective function of invariant NKT cells in a mouse model of innate-cell-driven lung inflammation.

    abstract::Activation of invariant natural killer T (iNKT) cells by treatment with their α-galactosyl ceramide ligand provides therapeutic benefits in several immune inflammatory settings. Given the artificial nature of this stimulation, the natural regulatory functions of iNKT remain uncertain. Addressing this issue in a mouse ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201040647

    authors: Bourgeois EA,Levescot A,Diem S,Chauvineau A,Bergès H,Milpied P,Lehuen A,Damotte D,Gombert JM,Schneider E,Girard JP,Gourdy P,Herbelin A

    更新日期:2011-02-01 00:00:00

  • Peptide recognition, T cell receptor usage and HLA restriction elements of human heat-shock protein (hsp) 60 and mycobacterial 65-kDa hsp-reactive T cell clones from rheumatoid synovial fluid.

    abstract::A commonly held postulate regarding the etiology of rheumatoid arthritis (RA) is that of antigenic mimicry. Recent interest has focused on the mycobacterial 65-kDa heat-shock protein (hsp) as a putative causal agent. The 65-kDa hsp has over 40% sequence homology with the human hsp 60, and elevated synovial T cell resp...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830220529

    authors: Quayle AJ,Wilson KB,Li SG,Kjeldsen-Kragh J,Oftung F,Shinnick T,Sioud M,Førre O,Capra JD,Natvig JB

    更新日期:1992-05-01 00:00:00

  • Visualizing the dynamic of adoptively transferred T cells during the rejection of large established tumors.

    abstract::Adoptive T-cell therapy (ATCT) can result in tumor rejection, yet the behavior and fate of the introduced T cells remain unclear. We developed a novel bioluminescence mouse model, which enabled highly sensitive detection of T-cell signals at the single-cell level. Transferred T cells preferentially accumulated within ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201141452

    authors: Charo J,Perez C,Buschow C,Jukica A,Czeh M,Blankenstein T

    更新日期:2011-11-01 00:00:00

  • Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in non-obese diabetic mice.

    abstract::Lymphocyte infiltration to pancreatic islets is associated to chemoattraction, as are other inflammatory autoimmune processes. We examined whether development of insulitis and diabetes depends on chemoattraction of lymphocytes via the CCR5 chemokine receptor. In non-obese diabetic (NOD) mice, a substantial fraction of...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200324285

    authors: Carvalho-Pinto C,García MI,Gómez L,Ballesteros A,Zaballos A,Flores JM,Mellado M,Rodríguez-Frade JM,Balomenos D,Martínez-A C

    更新日期:2004-02-01 00:00:00

  • Granzyme B and perforin can be used as predictive markers of acute rejection in heart transplantation.

    abstract::We have investigated perforin and granzyme B expression in graft-infiltrating lymphocytes of patients who underwent heart transplantation. Those proteins are commonly present in the cytoplasmic granules of cytotoxic T lymphocytes and are released upon effector-target cell interaction. From 28 patients 103 endomyocardi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830240136

    authors: Legros-Maïda S,Soulié A,Benvenuti C,Wargnier A,Vallée N,Berthou C,Guillet J,Sasportes M,Sigaux N

    更新日期:1994-01-01 00:00:00

  • Dimerization of Fab fragments enables ready screening of phage antibodies that affect hepatocyte growth factor/scatter factor activity on target cells.

    abstract::A number of applications of antibodies in diagnosis and therapy require multivalent reagents either because of the polymeric nature of the antigens or because biological activity depends on an effect on the formation of homodimeric species. Here, we report a procedure for mass screening of phage-derived monomeric anti...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830270307

    authors: Zaccolo M,Griffiths AP,Prospero TD,Winter G,Gherardi E

    更新日期:1997-03-01 00:00:00

  • TWEAK can induce cell death via endogenous TNF and TNF receptor 1.

    abstract::TWEAK is a recently cloned novel member of the TNF ligand family. Here we show that soluble TWEAK is sufficient to induce apoptosis in Kym-1 cells within 18 h. TWEAK-induced apoptosis is indirect and is mediated by the interaction of endogenous TNF and TNF receptor (TNFR)1, as each TNFR1-Fc, neutralizing TNF-specific ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199906)29:06<1785::AID-IMM

    authors: Schneider P,Schwenzer R,Haas E,Mühlenbeck F,Schubert G,Scheurich P,Tschopp J,Wajant H

    更新日期:1999-06-01 00:00:00

  • The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them.

    abstract::F1----parental bone marrow chimeras between CBA and B10 mice were used to show that even after 1 year follicular dendritic cells (FDC), also termed dendritic reticular cells, are not derived from bone marrow stem cells. However clusters of cells wrapped in the dendritic processes of FDC, isolated by enzyme digestion o...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830140916

    authors: Humphrey JH,Grennan D,Sundaram V

    更新日期:1984-09-01 00:00:00

  • Activation of the alternative complement pathway by human B cell lymphoma lines is associated with Epstein-Barr virus transformation of the cells.

    abstract::Activation of the alternative complement pathway by human B cell lymphoma lines is correlated with the presence of Epstein Barr virus (EBV) in the cell genome. EBV-negative B cell lymphoma lines produce little activation of the alternative pathway as measured either by C3 deposition on the cell surface or C3 conversio...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830080702

    authors: McConnell I,Klein G,Lint TF,Lachmann PJ

    更新日期:1978-07-01 00:00:00

  • New vistas on macrophage differentiation and activation.

    abstract::Plasticity and heterogeneity are hallmarks of myelomonocytic differentiation and polarized activation. Evidence published in this issue of the European Journal of Immunology, together with other recent data, add new elements and perspectives to the current understanding of mononuclear phagocyte differentiation and act...

    journal_title:European journal of immunology

    pub_type: 评论,杂志文章,评审

    doi:10.1002/eji.200636910

    authors: Mantovani A,Sica A,Locati M

    更新日期:2007-01-01 00:00:00