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Garlanda C.,Humanitas Clinical and Research Center | Dinarello C.A.,Aurora University | Dinarello C.A.,Radboud University Nijmegen | Mantovani A.,Humanitas Clinical and Research Center | Mantovani A.,University of Milan
Immunity | Year: 2013

Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes seven ligands with agonist activity (IL-1α and IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ), three receptor antagonists (IL-1Ra, IL-36Ra, IL-38), and an anti-inflammatory cytokine (IL-37). Members of the IL-1 Receptor (IL-1R) family include six receptor chains forming four signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP), and two negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor antagonists, decoy receptors, and signaling inhibitors ensures a balance between amplification of innate immunity and uncontrolled inflammation. All cells of the innate immune system express and/or are affected by IL-1 family members. Moreover, IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells. Here we will review the key properties of IL-1 family members, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity. © 2013 Elsevier Inc. Source


Selmi C.,Humanitas Clinical and Research Center | Selmi C.,University of Milan
Autoimmunity Reviews | Year: 2014

Uveitis is the most common ophthalmological finding in the practice of rheumatology and clinical immunology. The condition is frequently idiopathic and defined by the inflammatory status of the uvea, the part of the middle eye that includes the iris, ciliary body and choroid. Anterior uveitis involves the iris and ciliary body, while the posterior form is limited to the retina and choroid. Both forms represent indications for an urgent evaluation by an ophthalmologist as untreated cases may cause blindness. Anterior uveitis is associated with the HLA-B27 allele and is a classification criterion for seronegative arthritis forms such as ankylosing spondylitis, psoriatic arthropathy, arthritis associated with Crohn's disease and ulcerative colitis, and reactive arthritis. Posterior uveitis is associated with Behcet's disease and HLA-B51. The clinical suspicion is raised by self-reported symptoms in the case of anterior involvement and floaters for posterior uveitis while the diagnosis, in the absence of established criteria, is made by an experienced ophthalmologist. © 2014 Elsevier B.V. Source


Graham G.J.,University of Glasgow | Locati M.,University of Milan | Locati M.,Humanitas Clinical and Research Center
Journal of Pathology | Year: 2013

Chemokines and their receptors are key regulators of leukocyte migration and intra-tissue accumulation under both homeostatic and inflammatory conditions. Regulation of chemokine-dependent responses, particularly those relating to inflammation, is essential to avoid the development of inflammatory and autoimmune pathologies. Recently, a new subfamily of chemokine receptors referred to as the 'atypical' chemokine receptors has emerged, members of which have been shown to play important roles in controlling in vivo chemokine biology. Here we review the basic biology of the chemokine and chemokine receptor family, introduce the topic of 'atypical' chemokine receptor biology and focus specifically on the best-characterized of the 'atypical' chemokine receptors, D6. D6 is a 'scavenging' receptor for inflammatory CC chemokines and plays a central role in the resolution of in vivo inflammatory responses. We describe the biology, biochemistry and pathological relevance of D6 and outline emerging data suggesting that it has additional important roles in integrating innate and adaptive immune responses. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source


Fries W.,Humanitas Clinical and Research Center
Current drug targets | Year: 2013

Inflammatory bowel diseases (IBD) are considered barrier diseases. After misleading initial results, the pathogenic importance of a disturbed mucosa is now widely accepted, largely because a certain percentage of first-degree relatives of patients with IBD do have permeability alterations, as assessed by oral markers. In the presence of a normal appearing gut mucosa, functional alterations of the highly dynamic inter-enterocyte tight junctions have to be considered to be responsible for the observed alterations. Indeed, various alterations of the transmembrane and intracytoplasmic proteins have been reported in IBD. An important therapeutic goal is to maintain disease remission by preservation of the correct organization of these complexes. Of the potential therapeutic approaches, the various anti-TNF agents are the best-studied agents, but other treatments may tighten the gut through as yet unknown mechanisms. Source


Selmi C.,Humanitas Clinical and Research Center | Selmi C.,University of Milan | Gershwin M.E.,University of California at Davis
Autoimmunity Reviews | Year: 2014

Reactive arthritis is a form of seronegative spondyloarthritis clinically associated with inflammatory back pain, additive or migratory oligoarthritis, and extra-articular symptoms that typically follow a gastrointestinal or urogenital infection by a minimum of 1 to a maximum of 3-6. weeks. Once arthritis is observed, however, microbial tests and blood or synovial fluid cultures are negative, and only serum antibodies are detected. Reactive arthritis commonly affects young adults, most frequently white and carrying the HLA-B27 allele. The genetic susceptibility appears as necessary with only 1-15% of cases of infection developing reactive arthritis. Clinical symptoms are different from septic arthritis which manifests with fever, systemic signs of infection, and monoarthritis. The presence of large joint oligoarthritis, urogenital tract infection, and uveitis characterizes Reiter's syndrome as a clinical subtype. Ocular, skin, and heart involvement are not uncommon and may be largely variable in severity. Diagnostic criteria are based on the ACR guidelines and include rheumatological signs along with a proof of infection. © 2014 Elsevier B.V. Source

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