Discussion| Volume 30, ISSUE 3, P323-328, May 2012

Abnormal epidermal barrier in the pathogenesis of psoriasis


      Almost 2 decades ago, Williams and Elias suggested a unifying concept for the pathogenesis of disorders of cornification, according to which the integrity of the epidermal barrier and its effective function is an important factor in the regulation of epidermal DNA synthesis. Interference with the barrier integrity or function will result in epidermal hyperplasia and may be the primary event leading to hyperproliferative skin diseases, such as psoriasis.
      We have analyzed alterations to several structures of the epidermal barrier that might be responsible for barrier dysfunction and thus lead to hyperproliferation of the epidermis in an attempt to repair the barrier and, as a result, might be inducers of psoriasis. There are several convincing reports indicating that inhibiting of epidermal transglutaminase may lead to epidermal hyperproliferation and that this stimulus might trigger psoriasis among genetically predisposed patients.
      Disturbance of epidermal barrier function caused by derangement of lipid or cholesterol or ceramide synthesis leads to increased DNA synthesis and epidermal hyperplasia and as a result might be an inducer of psoriasis. We could find little evidence to show that defective defense of the epidermis or an abnormal response of it to bacteria plays a role in the pathogenesis of psoriasis.
      Accumulating data indicate that there is an association of psoriasis and mutations of genes within the epidermal differentiation complex, which are crucial for the development, maturation, cornification, cross-linking, and terminal differentiation of the epidermis, called psoriasis susceptibility locus 4.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinics in Dermatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Nickoloff B.J.
        • Wrone-Smith T.
        • Bonish B.
        • et al.
        Response of murine and normal human skin to injection of allogeneic blood-derived psoriatic immunocytes: detection of T cells expressing receptors typically present on natural killer cells, including CD94, CD158, and CD161.
        Arch Dermatol. 1999; 135: 546-552
        • Nickoloff B.J.
        • Schröder J.M.
        • von den D.P.
        • et al.
        Is psoriasis a T-cell disease?.
        Exp Dermatol. 2000; 9: 359-375
        • Daikeler T.
        • Gunaydin I.
        • Einsele H.
        • et al.
        Transmission of psoriatic arthritis by allogeneic bone marrow transplantation for chronic myelogenous leukaemia from an HLA-identical donor.
        Rheumatology (Oxford). 1999; 38: 89-90
        • Gardembas-Pain M.
        • Ifrah N.
        • Foussard C.
        • et al.
        Psoriasis after allogeneic bone marrow transplantation.
        Arch Dermatol. 1990; 126: 1523
        • Snowden J.A.
        • Heaton D.C.
        Development of psoriasis after syngeneic bone marrow transplant from psoriatic donor: further evidence for adoptive autoimmunity.
        Br J Dermatol. 1997; 137: 130-132
        • He Y.L.
        • Lu X.J.
        • Qiu J.Y.
        • et al.
        Severe vulgaris psoriatic patients with acute myelogenous leukaemia and resolution after allogeneic bone marrow transplantation/peripheral blood stem cell transplantation.
        Chin Med J (Engl ). 2005; 118: 861-865
        • Kanamori H.
        • Tanaka M.
        • Kawaguchi H.
        • et al.
        Resolution of psoriasis following allogeneic bone marrow transplantation for chronic myelogenous leukemia: case report and review of the literature.
        Am J Hematol. 2002; 71: 41-44
        • Zenz R.
        • Eferl R.
        • Kenner L.
        • et al.
        Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins.
        Nature. 2005; 437: 369-375
        • Guinea-Viniegra J.
        • Zenz R.
        • Scheuch H.
        • et al.
        TNFalpha shedding and epidermal inflammation are controlled by Jun proteins.
        Genes Dev. 2009; 23: 2663-2674
        • Sano S.
        • Chan K.S.
        • Carbajal S.
        • et al.
        Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model.
        Nat Med. 2005; 11: 43-49
        • Williams M.L.
        • Elias P.M.
        From basket weave to barrier. Unifying concepts for the pathogenesis of the disorders of cornification.
        Arch Dermatol. 1993; 129: 626-629
        • Elias P.M.
        Stratum corneum defensive functions: an integrated view.
        J Invest Dermatol. 2005; 125: 183-200
        • Eckert R.L.
        • Sturniolo M.T.
        • Broome A.M.
        • et al.
        Transglutaminase function in epidermis.
        J Invest Dermatol. 2005; 124: 481-492
        • Hitomi K.
        Transglutaminases in skin epidermis.
        Eur J Dermatol. 2005; 15: 313-319
        • Schmuth M.
        • Gruber R.
        • Elias P.M.
        • et al.
        Ichthyosis update: towards a function-driven model of pathogenesis of the disorders of cornification and the role of corneocyte proteins in these disorders.
        Adv Dermatol. 2007; 23: 231-256
        • Wolf R.
        • Ruocco V.
        Triggered psoriasis.
        Adv Exp Med Biol. 1999; 455: 221-225
        • Wolf R.
        • Lo Schiavo A.
        • Lombardi M.L.
        • et al.
        The in vitro effect of hydroxychloroquine on skin morphology and transglutaminase.
        Int J Dermatol. 1997; 36: 704-707
        • Wolf R.
        • Lo Schiavo A.
        • Lombardi M.L.
        • et al.
        The in vitro effect of hydroxychloroquine on skin morphology in psoriasis.
        Int J Dermatol. 1999; 38: 154-157
        • Harrison C.A.
        • Layton C.M.
        • Hau Z.
        • et al.
        Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue-engineered skin.
        Br J Dermatol. 2007; 156: 247-257
        • Elias P.M.
        • Williams M.L.
        • Maloney M.E.
        • et al.
        Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis.
        J Clin Invest. 1984; 74: 1414-1421
        • Proksch E.
        • Feingold K.R.
        • Man M.Q.
        • et al.
        Barrier function regulates epidermal DNA synthesis.
        J Clin Invest. 1991; 87: 1668-1673
        • Grubauer G.
        • Elias P.M.
        • Feingold K.R.
        Transepidermal water loss: the signal for recovery of barrier structure and function.
        J Lipid Res. 1989; 30: 323-333
        • Feingold K.R.
        • Man M.Q.
        • Proksch E.
        • et al.
        The lovastatin-treated rodent: a new model of barrier disruption and epidermal hyperplasia.
        J Invest Dermatol. 1991; 96: 201-209
        • Wolf R.
        • Lo Schiavo A.
        • Russo A.
        • et al.
        Effects of gemfibrozil on in vitro cultured normal human skin explants.
        Int J Dermatol. 1999; 38: 65-69
        • Choi M.J.
        • Maibach H.I.
        Role of ceramides in barrier function of healthy and diseased skin.
        Am J Clin Dermatol. 2005; 6: 215-223
        • Wartewig S.
        • Neubert R.H.
        Properties of ceramides and their impact on the stratum corneum structure: a review. Part 1:ceramides.
        Skin Pharmacol Physiol. 2007; 20: 220-229
        • Jensen J.M.
        • Proksch E.
        The skin's barrier.
        G Ital Dermatol Venereol. 2009; 144: 689-700
        • Motta S.
        • Monti M.
        • Sesana S.
        • et al.
        Ceramide composition of the psoriatic scale.
        Biochim Biophys Acta. 1993; 1182: 147-151
        • Motta S.
        • Sesana S.
        • Monti M.
        • et al.
        Interlamellar lipid differences between normal and psoriatic stratum corneum.
        Acta Derm Venereol Suppl (Stockh). 1994; 186: 131-132
        • Motta S.
        • Monti M.
        • Sesana S.
        • et al.
        Abnormality of water barrier function in psoriasis. Role of ceramide fractions.
        Arch Dermatol. 1994; 130: 452-456
        • Alessandrini F.
        • Pfister S.
        • Kremmer E.
        • et al.
        Alterations of glucosylceramide-beta-glucosidase levels in the skin of patients with psoriasis vulgaris.
        J Invest Dermatol. 2004; 123: 1030-1036
        • Hong K.K.
        • Cho H.R.
        • Ju W.C.
        • et al.
        A study on altered expression of serine palmitoyltransferase and ceramidase in psoriatic skin lesion.
        J Korean Med Sci. 2007; 22: 862-867
        • Alessandrini F.
        • Stachowitz S.
        • Ring J.
        • et al.
        The level of prosaposin is decreased in the skin of patients with psoriasis vulgaris.
        J Invest Dermatol. 2001; 116: 394-400
        • Cho Y.
        • Lew B.L.
        • Seong K.
        • et al.
        An inverse relationship between ceramide synthesis and clinical severity in patients with psoriasis.
        J Korean Med Sci. 2004; 19: 859-863
        • Travers J.B.
        • Hamid Q.A.
        • Norris D.A.
        • et al.
        Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis.
        J Clin Invest. 1999; 104: 1181-1189
        • Roberson E.D.
        • Bowcock A.M.
        Psoriasis genetics: breaking the barrier.
        Trends Genet. 2010; 26: 415-423
        • Strange A.
        • Capon F.
        • Spencer C.C.
        • et al.
        A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
        Nat Genet. 2010; 42: 985-990
        • Stuart P.E.
        • Nair R.P.
        • Ellinghaus E.
        • et al.
        Genome-wide association analysis identifies three psoriasis susceptibility loci.
        Nat Genet. 2010; 42: 1000-1004
        • Sun L.D.
        • Cheng H.
        • Wang Z.X.
        • et al.
        Association analyses identify six new psoriasis susceptibility loci in the Chinese population.
        Nat Genet. 2010; 42: 1005-1009
        • Mischke D.
        • Korge B.P.
        • Marenholz I.
        • et al.
        Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21.
        J Invest Dermatol. 1996; 106: 989-992
        • Capon F.
        • Novelli G.
        • Semprini S.
        • et al.
        Searching for psoriasis susceptibility genes in Italy:genome scan and evidence for a new locus on chromosome 1.
        J Invest Dermatol. 1999; 112: 32-35
        • Capon F.
        • Semprini S.
        • Chimenti S.
        • et al.
        Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21.
        J Invest Dermatol. 2001; 116: 728-730
        • Liu Y.
        • Helms C.
        • Liao W.
        • et al.
        A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci.
        PLoS Genet. 2008; 4: e1000041
        • de Cid R.
        • Riveira-Munoz E.
        • Zeeuwen P.L.
        • et al.
        Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis.
        Nat Genet. 2009; 41: 211-215
        • Zhang X.J.
        • Huang W.
        • Yang S.
        • et al.
        Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21.
        Nat Genet. 2009; 41: 205-210
        • de Guzman S.C.
        • Conlan S.
        • Deming C.B.
        • et al.
        A milieu of regulatory elements in the epidermal differentiation complex syntenic block: implications for atopic dermatitis and psoriasis.
        Hum Mol Genet. 2010; 19: 1453-1460
        • Bergboer J.G.
        • Zeeuwen P.L.
        • Irvine A.D.
        • et al.
        Deletion of Late Cornified Envelope 3B and 3C genes is not associated with atopic dermatitis.
        J Invest Dermatol. 2010; 130: 2057-2061