Skin Basement Membrane Zone: A Depository for Circulating Microbial Antigen Evoking Psoriasis and Autoimmunity

Noah, Patricia W.; Handorf, Charles R.; Skinner, Robert B.; Mandrell, Timothy D.; Rosenberg, Elizabeth

doi:10.1111/j.1540-9740.2006.04277.x

Cited by 5 publications

(3 citation statements)

References 37 publications

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“…13,14 However, the role of ECM proteins in the development of psoriatic epidermal lesions remains to be fully investigated. [15][16][17] Notably, however, McFadden et al have proposed a laminin-dependent mechanism by which self-limiting guttate psoriasis caused by streptococcal pharyngitis develops to chronic psoriasis. Briefly, streptokinase, which is produced by streptococci, can initiate lysis and disruption of laminin.…”

Section: Introductionmentioning

confidence: 99%

Re-investigating the Basement Membrane Zone of Psoriatic Epidermal Lesions: Is Laminin-511 a New Player in Psoriasis Pathogenesis?

Natsumi

Sugawara

Yasumizu

et al. 2018

J Histochem Cytochem.

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Psoriasis is a complex chronic inflammatory skin disease characterized by epidermal thickening on the basis of increased keratinocyte proliferation and insufficient apoptosis. Laminins are important components of the basement membrane (BM) and impact on epidermal keratinocyte growth/apoptosis. Although several laminins are involved in the pathogenesis of psoriasis, it is still controversial about the expression patterns of laminin isoforms and which laminins are important in the development of psoriasis. Because laminin-511 and -332 are key BM components in human skin, and laminin-511 stimulates human hair follicle growth, we asked whether the BM zone in psoriasis shows any laminin-related abnormalities. This showed that the BM expression of laminin-511 and -332 was significantly increased within the skin lesion of psoriasis. Immunofluorescence microscopy revealed that laminin-511, -332, and collagen type IV proteins were also significantly increased in psoriasis-like skin lesions of Imiquimod-treated mice. Transmission electron microscopy showed a few gaps of lamina densa, and its thickness was significantly increased. Finally, laminin-511 treatment significantly stimulated the proliferation and inhibited apoptosis of HaCaT cells, while laminin-α5 chain gene knockdown decreased proliferation and induced apoptosis. These phenomenological observations raise the question of whether laminin-511-controlled keratinocyte growth/death may be a previously overlooked player in the pathogenesis of psoriatic epidermal lesions.

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Section: Introductionmentioning

confidence: 99%

Re-investigating the Basement Membrane Zone of Psoriatic Epidermal Lesions: Is Laminin-511 a New Player in Psoriasis Pathogenesis?

Natsumi

Sugawara

Yasumizu

et al. 2018

J Histochem Cytochem.

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“…The compartments mostly affected during PsA, namely, the skin, joints, and entheses, are likely sites where bacterial components are preferentially deposited (13–15). In synovial fluid from PsA patients, a higher variety and concentration of bacterial DNAs were found compared to serum (13). The trapping of microbial products at specific compromised sites appears indicative of at least a perpetuating role for pathogens in PsA.…”

mentioning

confidence: 99%

Impaired dendritic cell proinflammatory cytokine production in psoriatic arthritis

Wenink¹,

Santegoets²,

Butcher³

et al. 2011

Arthritis & Rheumatism

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Objective. The pathogenesis of psoriatic arthritis (PsA) remains poorly understood. The underlying chronic inflammatory immune response is thought to be triggered by unknown environmental factors potentially arising from a defective immune function. We undertook this study to determine whether an impaired acute inflammatory response by dendritic cells (DCs) might compromise the clearance of bacteria and predispose to chronic inflammation.Methods. We determined cytokine production by DCs from healthy controls and from patients with rheumatoid arthritis, PsA, and psoriasis in response to Mycobacterium tuberculosis, Mycobacterium avium paratuberculosis, and a range of other bacteria and Toll-like receptor (TLR) ligands. Phenotypic differences involved in cellular responses against (myco)bacteria were determined by quantitative polymerase chain reaction and flow cytometry.Results. The secretion of proinflammatory cytokines by PsA DCs was impaired upon in vitro challenge with mycobacteria and TLR-2 ligands. This impairment was associated with elevated serum levels of C-reactive protein. The expression of TLR-2 and other receptors known to mediate mycobacterial recognition was unaltered. In contrast, the intracellular TLR inhibitors suppressor of cytokine signaling 3 and A20 were more highly expressed in DCs from PsA patients. PsA DCs further demonstrated up-regulated levels of ATG16L1, NADPH oxidase 2, and LL37, which are molecules implicated in the immune response against intracellular bacteria.Conclusion. Our findings indicate that DCs from PsA patients have a disordered immune response toward some species of (myco)bacteria. This might predispose to impaired immune responses to, and in turn impaired clearance of, these bacteria, setting the stage for the chronic inflammation of joints, entheses, skin, and the gut.Psoriatic arthritis (PsA) is a common heterogeneous inflammatory disease of the skin, joints, and entheses leading to discomfort and pain and, in some cases, the aggressive destruction of joints (1-3). Like other spondylarthritides, PsA is associated with HLA-B27 positivity and (sub)clinical eye and gut inflammation (1). Although the pathogenesis of PsA is unclear, the underlying chronic inflammatory immune response, as in psoriasis, might be triggered by unknown environmental factors that function on the background of a polygenic susceptibility.

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“…These may leak into circulation, evoke specific immune response and eventually may be deposited along the skin basement membrane zone, which is believed to be the first step of their percutaneous elimination. If microbial antigens share structural homologies with skin components (molecular mimicry), the additional result may be the development of antigenantibody complexes, cross-reactive antibodies or specific T cells cross-reacting against epidermal autoantigens [24,25]. For example, molecular mimicry between H. pylori antigens and keratin 17 may result in activation of autoreactive T cells and augment keratinocyte hyperproliferation [22].…”

Section: Discussionmentioning

confidence: 99%

Psoriasis vulgaris and digestive system disorders: is there a linkage?

Pietrzak

Jastrzębska²,

Chodorowska³

et al. 2010

Folia Histochem Cytobiol.

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Psoriasis is well-known immune-mediated skin disease often associated with co-morbidities, including dyslipidaemia and obesity. Few reports imply that the disease might be also related to pathology of mucosal surfaces, especially that of the digestive system. The authors present a case of psoriasis and concurrent digestive system abnormalities, and review the literature regarding the topic. A 40-year-old man suffered from an exacerbation of exudative psoriasis for about 6 months. Topical antipsoriatics proved ineffective and the disease gradually progressed to a severe disseminated form. Subsequent detailed examinations revealed persistent gastroduodenitis due to H. pylori infection, pancreatic dysfunction and fatty change of the liver, although the patient denied any gastrointestinal symptoms. As a result appropriate treatment of the diagnosed digestive system disorders was added to topical antipsoriatic therapy. Within 2 weeks of treatment clinical symptoms and laboratory signs showed a marked trend to normalisation. The presented medical history seems to suggest that there may be some kind of interplay between psoriasis and digestive system disorders.

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Skin Basement Membrane Zone: A Depository for Circulating Microbial Antigen Evoking Psoriasis and Autoimmunity

Cited by 5 publications

References 37 publications

Re-investigating the Basement Membrane Zone of Psoriatic Epidermal Lesions: Is Laminin-511 a New Player in Psoriasis Pathogenesis?

Re-investigating the Basement Membrane Zone of Psoriatic Epidermal Lesions: Is Laminin-511 a New Player in Psoriasis Pathogenesis?

Impaired dendritic cell proinflammatory cytokine production in psoriatic arthritis

Psoriasis vulgaris and digestive system disorders: is there a linkage?

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