Autoantigens <scp>ADAMTSL</scp>5 and <scp>LL</scp>37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes

Fuentes‐Duculan, Judilyn; Bonifacio, Kathleen M.; Hawkes, Jason E.; Kunjravia, Norma; Cueto, Inna; Li, Xuan; Gonzalez, Juana; Garcet, Sandra; Krueger, James G.

doi:10.1111/exd.13378

Cited by 98 publications

(87 citation statements)

References 35 publications

(62 reference statements)

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“…LL37 and ADAMTSL5 are both potential antigens found at significantly higher concentrations in lesional skin, but they are also expressed by immune cells that are classically associated with psoriasis, namely, dendritic cells and macrophages [83]. These autoantigens also appear to be under the influence of well-established psoriatic treatment, with the concentration of ADAMTSL5 and LL37 downregulated by etanercept, ixekizumab, and brodalumab [83]. …”

Section: Resultsmentioning

confidence: 99%

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

2018

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Background: Psoriasis is a common, chronic inflammatory skin disorder, which can significantly impact quality of life. Despite major breakthroughs in our understanding of the pathogenesis of psoriasis, the chronological order of the underlying mechanisms leading to the development of psoriatic plaques remains to be completely understood. Summary: Although psoriasis is classically perceived as a T-cell disease, it is now well recognized that T lymphocytes do not function in exclusivity. This theory is supported by evidence from transgenic murine models that develop marked psoriasiform disease. In addition, immune cells and cytokines regulate both early and late events involved in the pathogenesis of psoriasis. Key Messages: Psoriasis is a complex disease – a dynamic interplay between immune cells, keratinocytes, and various other skin-resident cells, such as endothelial and immune cells. The contribution of each cell type is crucial in the initiation and maintenance phases of psoriatic alterations.

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Section: Resultsmentioning

confidence: 99%

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

2018

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“…34 Importantly, recent results from our laboratory suggest that the possibility of ADAMTSL5 antigen presentation and the subsequent activation of IL-17-producing T-cells in psoriatic skin may involve other immune cell populations, such as keratinocytes and dendritic cells. 37, 38 …”

Section: Psoriasis As a T-cell Mediated Autoimmune Conditionmentioning

confidence: 99%

“…Unfortunately, little is known about the exact immune events leading to the loss of immune tolerance in individuals susceptible to psoriasis. It is essential that future studies further explore these molecular mechanisms and carefully characterize the expression profiles of potential autoantigens in all cell types found in the skin and blood of psoriasis patients, 38 as well as their relationship to major psoriasis susceptibility loci.…”

Section: Psoriasis As a T-cell Mediated Autoimmune Conditionmentioning

confidence: 99%

Psoriasis pathogenesis and the development of novel targeted immune therapies

Hawkes

Chan

Krueger

2017

Journal of Allergy and Clinical Immunology

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709

605

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Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, psoriasis autoantigens, and multiple environmental factors. Over the last two decades, research has unequivocally shown that psoriasis represents a bona fide T-cell mediated disease primarily driven by pathogenic T-cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/T17 cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition. The activation and upregulation of IL-17 in pre-psoriatic skin produces a “feed forward” inflammatory response in keratinocytes that is self-amplifying and drives the development of mature psoriatic plaques by inducing epidermal hyperplasia, epidermal cell proliferation, and the recruitment of leukocyte subsets into the skin. Clinical trial data for monoclonal antibodies against IL-17 signaling (secukinumab, ixekizumab, and brodalumab) and newer IL-23p19 antagonists (tildrakizumab, guselkumab, and risankizumab) underscore the central role of these cytokines as predominant drivers of psoriatic disease. We are currently witnessing a translational revolution in the treatment and management of psoriasis. Emerging bispecific antibodies offer the potential for even better disease control, while small molecule drugs may offer future alternatives to the use of biologics and less costly long-term disease management.

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“…It was recently shown that CD8+ T cells respond to peptides derived from the ADAMTSL5 protein in a HLA-Cw*0602 restricted fashion, resulting in release of IL-17A and IFN-γ[17]. All three of these putative autoantigens in psoriasis are strongly induced in psoriatic skin[18,19], with LL-37 and ADAMTSL5 having fairly widespread expression patterns[19], but keratin 17 expression is limited to the psoriatic epidermis[18]. …”

Section: Genetics Adaptive Immune System and Evidence For Autoimmunimentioning

confidence: 99%

Psoriasis: a mixed autoimmune and autoinflammatory disease

Liang

Sarkar

Tsoi

et al. 2017

Current Opinion in Immunology

184

140

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In recent years marked progress has been made in our understanding of the critical biologic and immunologic pathways involved in psoriasis. Genetic studies have demonstrated that susceptibility to psoriasis involves components of both the adaptive and innate immune system and not surprisingly activation of both of these arms of the immune system is found in psoriatic skin. While adaptive immune responses predominate in chronic plaque psoriasis, innate and autoinflammatory responses dominate in pustular forms of psoriasis, with other clinical subtypes extending on a spectrum between plaque and pustular psoriasis. This makes psoriasis a unique disease where both autoimmune and autoinflammatory responses co-exist, with the balance between the two being critical in shaping its clinical presentation.

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Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes

Cited by 98 publications

References 35 publications

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

Psoriasis pathogenesis and the development of novel targeted immune therapies

Psoriasis: a mixed autoimmune and autoinflammatory disease

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