Genome-Wide Meta-Analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL

Ellinghaus, Eva; Stuart, Philip E.; Ellinghaus, David; Nair, Rajan P.; Debrus, Sophie; Raelson, John; Belouchi, Majid; Tejasvi, Trilokraj; Liu, Yanming; Tsoi, Lam C.; Onken, Anna Theresa; Esko, Tõnu; Metspalu, Andres; Rahman, Proton; Gladman, Dafna D.; Bowcock, Anne M.; Helms, Cynthia; Krueger, Gerald G.; Kõks, Sulev; Kingo, Külli; Gieger, Christian; Wichmann, Heinz‐Erich; Mrowietz, Ulrich; Weidinger, Stephan; Schreiber, Stefan; Abecasis, Gonçalo R.; Elder, James T.; Weichenthal, Michael; Franke, André

doi:10.1038/jid.2011.415

Cited by 110 publications

(66 citation statements)

References 38 publications

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“…Because 80% of the patients develop PsA following psoriasis (Ellinghaus et al 2012b), PsA is sometime considered as a disease within a disease (Eder et al 2011). In keeping with this, several PsA susceptibility genes, such as HLA-C, IL-12B, IL-23R, TNIP1 overlap with psoriasis (Liu et al 2008;Huffmeier et al 2010;Ellinghaus et al 2012b).…”

Section: Psoriatic Arthritismentioning

confidence: 99%

“…In keeping with this, several PsA susceptibility genes, such as HLA-C, IL-12B, IL-23R, TNIP1 overlap with psoriasis (Liu et al 2008;Huffmeier et al 2010;Ellinghaus et al 2012b). On the other hand, differences in the genetic background of the two conditions do exist and unique genetic determinants have been identified, although not at genome-wide significance (Liu et al 2008).…”

Section: Psoriatic Arthritismentioning

confidence: 99%

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Psoriasis

Meglio

Villanova

Nestle

2014

Cold Spring Harbor Perspectives in Medicine

269

202

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Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life.This skin is me, I can't get out.

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Section: Psoriatic Arthritismentioning

confidence: 99%

Section: Psoriatic Arthritismentioning

confidence: 99%

Psoriasis

Meglio

Villanova

Nestle

2014

Cold Spring Harbor Perspectives in Medicine

269

202

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“…SNPs in STAT3 have been linked to many of the same human autoimmune diseases associated with the IL-23 pathway, including psoriasis, IBD, and ankylosing spondylitis (66)(67)(68). Loss-of-function mutations in STAT3 lead to the development of autosomal-dominant hyper-IgE syndrome, manifestations of which include chronic mucocutaneous candidiasis and recurrent staphylococcal infections.…”

Section: Cytokine Regulation Of Th17 Differentiationmentioning

confidence: 99%

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Burkett¹,

Hörste²,

Kuchroo³

2015

J. Clin. Invest.

204

137

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R e v i e w S e R i e S : A u t o i m m u n i t y2 2 1 2 jci.org Volume 125 Number 6 June 2015Murine Th17 differentiation can also be induced in the absence of TGF-β1 signaling, via the combination either of IL-1β, IL-6, and IL-23 or of 42). These TGF-β1-independent Th17 cells can efficiently induce autoimmune tissue inflammation upon adoptive transfer, a trait that led to them being termed "pathogenic" Th17 cells. Additionally, they possess a gene expression profile distinct from that of "nonpathogenic" Th17 cells, which are differentiated with TGF-β1 and IL-6. These observations have led to two competing hypotheses. The first posits that IL-23 cements Th17 lineage commitment such that Th17 cells induced with TGF-β1 and IL-6 are insufficiently committed to the lineage and cannot induce autoimmune tissue inflammation. The second suggests that there are distinct subtypes of Th17 cells whose differentiation is dependent on distinct combinations of cytokines. The latter hypothesis is supported by the finding that pathogenic Th17 cells express higher levels of several Th1 lineage-associated transcripts, such as the transcription factor T-bet and IFN-γ, and have been shown to be derived from IL-17 single producers by fate mapping experiments (43,44). Similarly, an important feature of human Th17 cells, as well as those isolated from inflamed tissues in mouse models of Th17-mediated disease, is that they coproduce IL-17 with other cytokines, leading to distinct functional roles (45)(46)(47). For instance, human Th17 cells that produce both IL-10 and IL-17 preferentially respond to Staphylococcus aureus, while those that produce both IL-17 and IFN-γ recognize Candida albicans, suggesting that distinct pathogens induce distinct subtypes of Th17 cells (40). IL-17/IFN-γ coproducers have been ascribed pathogenic functions in the CNS during EAE; however, it has been difficult to reliably differentiate such cells in vitro. Repeated rounds of in vitro culture in the presence of either Th1-inducing cytokines or IL-23 can induce IL-17/IFN-γ coproducers, albeit at moderate percentages. The transcription factors T-bet, RUNX1, and RUNX3 appear to be important in the acquisition of this phenotype (48,49).Large-scale transcriptional analysis of Th17 differentiation at very high temporal resolution has begun to elucidate the molecular networks that control this process, and is a promising approach to the identification of novel regulatory molecules that control pathogenic Th17 differentiation (50, 51). In fact, Th17 development is controlled induction of this lineage. The combination of TGF-β1 and IL-6 efficiently induces IL-17-producing murine T cells in vitro and highlights the reciprocal relationship between induced Tregs, which are generated by TGF-β1 alone, and Th17 cells (19,20). A series of studies demonstrated that IL-21, a γ c -dependent cytokine, could promote the differentiation of Th17 cells (21-23). In combination with TGF-β, IL-21 induces IL-17 production from naive Th cells and promotes the expression of both RORγt, th...

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“…Our understanding of the genetic architecture of psoriasis has increased rapidly due to genome-wide association studies (GWASs), which have identified more than 40 psoriasis susceptibility genes/loci [2][3][4][5][6][7][8][9][10][11][12][13] . However, the combined effect of these loci does not fully account for the observed genetic susceptibility to psoriasis, indicating that additional genetic factors remain to be discovered.…”

mentioning

confidence: 99%