Journal ArticleDOI
Interleukin-36–Receptor Antagonist Deficiency and Generalized Pustular Psoriasis
Slaheddine Marrakchi,Philippe Guigue,Blair R. Renshaw,Anne Puel,Xue-Yuan Pei,Sylvie Fraitag,Jihen Zribi,Elodie Bal,Céline Cluzeau,Maya Chrabieh,Jennifer E. Towne,Jason Douangpanya,Christian Pons,Sourour Mansour,Valérie Serre,Hafedh Makni,Nadia Mahfoudh,Faiza Fakhfakh,Christine Bodemer,Josué Feingold,Smail Hadj-Rabia,Michel Favre,Emmanuelle Génin,Mourad Sahbatou,Arnold Munnich,Jean-Laurent Casanova,John E. Sims,Hamida Turki,Hervé Bachelez,Asma Smahi +29 more
TLDR
Aberrant interleukin-36Ra structure and function lead to unregulated secretion of inflammatory cytokines and generalized pustular psoriasis.Abstract:
Background Generalized pustular psoriasis is a life-threatening disease of unknown cause. It is characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein, which may be associated with plaque-type psoriasis. Methods We performed homozygosity mapping and direct sequencing in nine Tunisian multiplex families with autosomal recessive generalized pustular psoriasis. We assessed the effect of mutations on protein expression and conformation, stability, and function. Results We identified significant linkage to an interval of 1.2 megabases on chromosome 2q13-q14.1 and a homozygous missense mutation in IL36RN, encoding an interleukin-36–receptor antagonist (interleukin-36Ra), an antiinflammatory cytokine. This mutation predicts the substitution of a proline residue for leucine at amino acid position 27 (L27P). Homology-based structural modeling of human interleukin-36Ra suggests that the proli...read more
Citations
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Neutrophil extracellular traps in immunity and disease
TL;DR: The identification of molecules that modulate the release of NETs has helped to refine the view of the role of neutrophils in immune protection, inflammatory and autoimmune diseases and cancer.
Journal ArticleDOI
The Interleukin-1 Family: Back to the Future
TL;DR: The key properties of IL-1 family members are reviewed, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.
Journal ArticleDOI
Immunology of Psoriasis
TL;DR: The genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome are discussed.
Journal ArticleDOI
Overview of the IL-1 family in innate inflammation and acquired immunity.
TL;DR: Although the inflammatory properties of the IL‐1 family dominate in innate immunity, IL‐2 family member can play a role in acquired immunity and this overview is a condensed update.
Journal ArticleDOI
Psoriasis Pathogenesis and Treatment.
Adriana Rendon,Knut Schäkel +1 more
TL;DR: The role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis is described, which includes a comprehensive review of well-established widely available therapies and novel targeted drugs.
References
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TL;DR: The IL-1 family includes members that suppress inflammation, both specifically within the IL-2 family but also nonspecifically for TLR ligands and the innate immune response.
Journal ArticleDOI
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John E. Sims,Dirk E. Smith +1 more
TL;DR: This Review provides an overview of both the long-established and more recently characterized members of the IL-1 family and their effects on immune cells, their involvement in human disease and disease models is discussed.
Journal ArticleDOI
Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways
Rajan P. Nair,Kristina Callis Duffin,Cynthia Helms,Jun Ding,Philip E. Stuart,David E. Goldgar,Johann E. Gudjonsson,Yun Li,Trilokraj Tejasvi,Bing Jian Feng,Andreas Ruether,Stefan Schreiber,Michael Weichenthal,Dafna D. Gladman,Proton Rahman,Steven J. Schrodi,Sampath Prahalad,Sampath Prahalad,Stephen L. Guthery,Stephen L. Guthery,Judith Fischer,Wilson Liao,Pui-Yan Kwok,Alan Menter,G. Mark Lathrop,Carol Wise,Ann B. Begovich,John J. Voorhees,James T. Elder,James T. Elder,Gerald G. Krueger,Anne M. Bowcock,Gonçalo R. Abecasis +32 more
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