A Potential Role for Superantigens in the Pathogenesis of Psoriasis

Leung, Donald Y.M.; Walsh, Patrick; Giorno, Ralph; Norris, David A.

doi:10.1111/1523-1747.ep12468941

Cited by 190 publications

(110 citation statements)

References 24 publications

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“…CM, culture medium. dermatitis (21), psoriasis (22), Kawasaki syndrome (23), and acute rheumatic fever (24). A unique feature of superantigens is that they possess particular structural and sequence characteristics that result in the shared ability to bypass the mechanisms of conventional, MHC-restricted Ag processing (25).…”

Section: Discussionmentioning

confidence: 99%

Bacterial Superantigens Enhance the In Vitro Proinflammatory Response and In Vivo Lethality of the TLR2 Agonist Bacterial Lipoprotein

Kearney

Wang

Redmond

et al. 2011

The Journal of Immunology

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Bacterial superantigens are Gram-positive exotoxins that induce proinflammatory cytokine release in vitro, cause lethal shock in vivo, and can be detected in the bloodstream of critically ill patients. They also have a powerful priming effect on the TLR4 agonist LPS. The aim of this study was to investigate the relationship between superantigens and the TLR2 agonist bacterial lipoprotein (BLP). Priming of human monocytes or PBMCs with superantigens significantly enhanced proinflammatory cytokine TNF-α and IL-6 release in response to BLP stimulation. The priming effect of superantigens could be blocked by inhibiting p38 MAPK during the priming phase as opposed to NF-κB or ERK inhibition. This was consistent with higher expression of the phosphorylated p38 after superantigen priming and BLP or LPS stimulation. C57BL/6 mice with superantigen priming (10 μg/mouse) when challenged with BLP (600 μg/mouse) exhibited substantially higher mortality (100%) compared with mice without superantigen priming (zero). Mice given superantigen alone did not demonstrate any signs of illness. Mice challenged with both superantigen and BLP had significantly higher levels of serum TNF-α and IL-6 compared with those of mice challenged with either agent alone. Depletion of the monocyte/macrophage subpopulation significantly reduced the mortality rate from 100 to 20% in superantigen-primed, BLP-challenged C57BL/6 mice, with a 5- to 10-fold decrease in serum TNF-α and IL-6. Our results demonstrate that bacterial superantigens enhance the in vitro proinflammatory cytokine release and in vivo lethality of BLP. This novel finding may help to explain the massive proinflammatory cytokine release seen in superantigen-mediated septic shock.

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Section: Discussionmentioning

confidence: 99%

Bacterial Superantigens Enhance the In Vitro Proinflammatory Response and In Vivo Lethality of the TLR2 Agonist Bacterial Lipoprotein

Kearney

Wang

Redmond

et al. 2011

The Journal of Immunology

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“…12,13 These T lymphocytes may be activated in these lesions by bacterial superantigens. 10,14,15 Cytotoxic T-lymphocytes (CTLs) are able to recognize and destroy tumor cells through the release of cytoplasmic granules, which contain TIA-1. TIA-1 is an intracellular 15 KD granule membrane-associated protein that can induce apoptotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the mononuclear inflammatory cell infiltrate in the nontumorigenic, Pretumorigenic and tumorigenic keratinocytic hyperproliferative lesions of the skin

Hussein¹,

Ahmed²

2005

Cancer Biology & Therapy

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Background: The keratinocytic hyperproliferative lesions include non-tumorigenic, pre-tumorigenic (actinic keratoses, AK), and tumorigenic (squamous cell carcinomas, SCC) conditions. Although mononuclear inflammatory cell infiltrate (MICs) is a constant feature in these lesions, their immunophenotypic characterization is still incomplete. We hypothesized that the development of non-tumorigenic, pre-tumorigenic, and tumorigenic keratinocytic hyperproliferative lesions is associated with alterations in the mononuclear inflammatory cell infiltrate in response to altered antigenicity of the lesional cells. This study tries to test this hypothesis and to characterize MICs in these lesions.Methods: Fifty lesions (non-tumorigenic lesions, 29; AK, 9 and SCC, 12) were examined using immunoperoxidase staining methods and antibodies targeting histiocytes (CD68), T cells (CD3), B cells (CD20), and T cells with cytotoxic potential (TIA-1).Results: As compared to the normal skin, the development of the keratinocytic hyperproliferative lesions (normal skin; non-tumorigenic; AK and SCC) was associated with a statistically significant increase(p = <0.05) in: (1) CD20 + B lymphocytes (0.0 ± 0.0 vs. 3.1 ± 0.5 vs. 7.5 ± 0.3 vs. 14.5 ± 5.5); (2) CD68 histiocytes (4.0 ± 1.0 vs. 26.5 ± 3.9 vs. 23 ± 1.9 vs. 41.3 ± 6.8); (3) CD3 + T lymphocytes (3.0 ± 1.1 vs. 58.3 ± 10.3 vs. 54.5 ± 0.2 vs. 41.0 ± 16.0); and (4) TIA-1 + cytotoxic T cells (1.8 ± 0.4 vs. 2.9 ± 0.7 vs. 9.6 ± 1.1 vs. 13.7 ± 5.2).Conclusions: The increase in the number of infiltrating mononuclear cells in all pathologic lesions compared to normal skin may reflect increased antigenicity of the lesional cells. Both humoral and cell mediated immunity are involved in these lesions.

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“…However, it should be stressed that streptococci may not be the only microorganisms that induce or maintain the disease. Other possible candidates include Staphylococcus aureus, Candida albicans (Leung et al 1993) and Pityrosporum orbiculare (Baker et al 1997). The type of vaccines to be developed for combating Streptococcus pyogenes in psoriasis will have to be left to vaccinologists.…”

Section: Discussionmentioning

confidence: 99%