Expression of interleukin-17 is correlated with interferon-α expression in cutaneous lesions of lupus erythematosus

Oh, Sung Hee; Roh, Hyo Jin; Kwon, Jang-Woo; Lee, S. H.; Kim, J. Y.; Choi, Heung Jai; Lim, Beom Jin

doi:10.1111/j.1365-2230.2010.03996.x

Cited by 46 publications

(34 citation statements)

References 53 publications

(104 reference statements)

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“…Several reports have described the presence of IL-17 related activity or signals in DLE lesions by immunohistochemistry (Oh et al , 2011; Tanasescu et al , 2010) or in the serum of DLE patients (Balanescu et al , 2010). IL-17-related markers have also been reported as upregulated compared to healthy controls in the serum of SLE patients in some (Shah et al , 2010; Zhao et al , 2010), but not all (Brajac et al , 2010; Higgs et al , 2012)) studies.…”

Section: Discussionmentioning

confidence: 99%

Dominant Th1 and Minimal Th17 Skewing in Discoid Lupus Revealed by Transcriptomic Comparison with Psoriasis

Jabbari

Suárez‐Fariñas

Fuentes‐Duculan

et al. 2014

Journal of Investigative Dermatology

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Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus. Despite its high frequency in systemic lupus in addition to cases without extracutaneous manifestations, targeted treatments for DLE are lacking, likely due to a dearth of knowledge of the molecular landscape of DLE skin. Here, we profiled the transcriptome of DLE skin in order to identify signaling pathways and cellular signatures that may be targeted for treatment purposes. Further comparison of the DLE transcriptome to that of psoriasis, a useful reference given our extensive knowledge of molecular pathways in this disease, provided a framework to identify potential therapeutic targets. Although a growing body of data supports a role for IL-17 and Th17 cells in systemic lupus, we show a relative enrichment of IFN-γ-associated genes without that for IL-17-associated genes in DLE. Extraction of T cells from the skin of DLE patients identified a predominance of IFN-γ-producing Th1 cells and an absence of IL-17-producing Th17 cells, complementing the results from whole skin transcriptomic analyses. These data therefore support investigations into treatments for DLE that target Th1 cells or the IFN-γ signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Dominant Th1 and Minimal Th17 Skewing in Discoid Lupus Revealed by Transcriptomic Comparison with Psoriasis

Jabbari

Suárez‐Fariñas

Fuentes‐Duculan

et al. 2014

Journal of Investigative Dermatology

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“…Within the disease setting of JSLE the PBMCs may be similarly activated once they have migrated to disease affected organs. Notably, IL-17 + infiltrating T cells have previously been detected in the kidney’s of adult SLE patients [21] and IL-17A protein has been found in cutaneous lesions of adult SLE patients [22]. …”

Section: Discussionmentioning

confidence: 99%

The pro-inflammatory potential of T cells in juvenile-onset systemic lupus erythematosus

et al. 2014

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BackgroundT cells are important to systemic lupus erythematosus (SLE) disease progression. This study determined the pro-inflammatory potential of T cells within the rare condition juvenile-onset SLE (JSLE).MethodIL-17A and Th1/Th2-related cytokine concentrations were measured in plasma/serum from JSLE patients (n = 19, n = 11) and HC (n = 18, n = 7). IL17A, RORC, IL23 and IL23R mRNA were measured in peripheral blood mononuclear cells (PBMCs) from JSLE and healthy controls (HC) (n = 12). Th17-associated cytokine expression was analysed in the supernatant of CD3/CD28 activated JSLE (n = 7) and HC (n = 6) PBMCs.ResultsJSLE plasma IL-17A level (21.5 ± 5.2 pg/ml) was higher compared to HC (7.2 ± 2.5 pg/ml, p = 0.028). No differences were found in Th1/Th2 cytokines levels. IL = 17A (p = 0.022), IL-6 (p = 0.028) and IL-21 (p = 0.003) concentrations were increased in supernatants from activated JSLE PBMCs. IL-17 F (p = 0.50) and IL-22 (p = 0.43) were also increased but were not statistically significant. IL17A and IL23 mRNA was significantly higher in JSLE PBMCs (p = 0.018 and p = 0.01).ConclusionJSLE T cells have an increased ability to secrete Th17 associated cytokines once activated, which could contribute to the pro-inflammatory disease phenotype seen in these patients.

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“…It has been reported that serum IL-17 levels are also elevated in SLE patients compared to controls (Vincent et al, 2013; Wong et al, 2008) and the Th17 pathway has been shown to drive autoimmune responses in pre-clinical mouse models of lupus (Hsu et al, 2008; Jacob et al, 2009). More importantly, IL-17 and IL-17 producing cells are also been detected in kidney tissue and skin biopsies from SLE patients (Crispin et al, 2008; Oh et al, 2011; Yang et al, 2009), suggesting a possible role for IL-17 in the pathophysiology of SLE and a potential therapeutic option of using anti-IL-17A in treating patients with SLE.…”

Section: Role Of Il-17a In Autoimmune Diseasesmentioning

confidence: 99%

Interluekin-17A (IL17A)

Chen

Kolls

2017

Gene

137

119

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The discovery of the key roles of interleukin-17A (IL-17A) and IL-17A producing cells in inflammation, autoimmune diseases and host defense has led to the experimental targeting of the IL-17A pathway in animal models of diseases as well as in clinical trials in humans. These therapeutic agents include biological products that target IL-17A and IL-23, an upstream regulator of IL-17A production. IL-17A producing T helper cells (Th17 cells) are a distinct lineage from the Th1 and Th2 CD4+ lineages and have been suggested to represent a good drug target in certain inflammatory conditions. Targeting IL-17A has been proven to be a good approach as anti-IL-17A is FDA approved for the treatment of psoriasis in 2015. In host defense, IL-17A has been shown to be mostly beneficial against infection caused by extracellular bacteria and fungi. This review will overview the discovery of IL-17A, the receptors used by this cytokine and its role in mucosal immunity and inflammation.

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Expression of interleukin-17 is correlated with interferon-α expression in cutaneous lesions of lupus erythematosus

Abstract: Two major cytokines, IL-17A and IFN-α, may play roles in the pathogenesis of CLE. Their patterns of expression positively correlated with each other.

Cited by 46 publications

References 53 publications

Dominant Th1 and Minimal Th17 Skewing in Discoid Lupus Revealed by Transcriptomic Comparison with Psoriasis

Dominant Th1 and Minimal Th17 Skewing in Discoid Lupus Revealed by Transcriptomic Comparison with Psoriasis

The pro-inflammatory potential of T cells in juvenile-onset systemic lupus erythematosus

Interluekin-17A (IL17A)

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