1,721,175 research outputs found
Corrigendum to “Tregs and Th17 lymphocytes in human DYRK1A haploinsufficiency” [Immunol. Lett. 214 (2019) 52–54](S0165247819302342)(10.1016/j.imlet.2019.08.003)
No full textThe authors regret for not publishing the correct order of authors in the original article. The correct authorship is: Valencic E, Todaro F, Piscianz E, Sirchia F, Spinelli AM, Tommasini A, Badolato R, Faletra F. The authors apologise for the inconvenience caused
Mechanisms of WHIM syndrome
No full textWHIM syndrome is a genetically inherited disease that is characterized by chronic neutropenia, myelokathexis, hypogammaglobulinemia, recurrent infections and warts. The discovery of heterozygous mutations of CXCR4, a G-protein-coupled receptor that is required for normal hematopoiesis and lymphoid homeostasis, as a major cause of WHIM syndrome has revealed the pathogenesis of this rare disorder. The recent availability of drugs that inhibit CXCL12 binding to its receptor CXCR4 has provided an attractive pathogenesis-driven therapeutic option for this disease. © 2005 Elsevier Ltd. All rights reserved
Uncovering an IL-10-dependent NF-{kappa}B recruitment to the IL-1ra promoter that is impaired in STAT3 functionally defective patients
No full textThe interleukin 1 receptor antagonist (IL-1ra) is an important negative regulator of the inflammatory response, whose genetic deficiency has been recently shown to cause a severe autoinflammatory syndrome in humans. In this study we characterized the molecular mechanisms whereby interleukin 10 (IL-10) potentiates IL-1ra transcription in LPS-stimulated monocytes and neutrophils. Using chromatin immunoprecipitation, we show that although NF-kappaBp65 and NF-kappaBp50 proteins accumulate into the nuclei and bind to the IkappaBalpha promoter during LPS stimulation, they are not recruited to the kappaB sites of the IL-1ra promoter. However, in response to LPS plus IL-10, which were found to induce chromatin acetylation, recruitment of both NF-kappaBp65 and NF-kappaBp50 to the IL-1ra promoter efficiently occurs in a STAT3-dependent manner. Accordingly, in neutrophils from hyper-IgE syndrome patients, who carry a nonfunctional STAT3, IL-10 failed to promote NF-kappaBp65 recruitment to the IL-1ra promoter and consequently to potentiate LPS-induced IL-1ra transcription. Altogether our findings uncover a novel mechanism whereby IL-10-activated STAT3 modulates IL-1ra transcription in LPS-treated phagocytes by making IL-1ra promoter accessible to readily available nuclear NF-kappaB.-Tamassia, N., Castellucci, M., Rossato, M., Gasperini, S., Bosisio, D., Giacomelli, M., Badolato, R., Cassatella, M. A., Bazzoni, F. Uncovering an IL-10-dependent NF-kappaB recruitment to the IL-1ra promoter that is impaired in STAT3 functionally defective patients
LE/shmania major. Infection of human monocytes selectively induces production of chemokines
No full textLeishmania are obligate intracellular parasites of monocytes, that may cause systemic disease or skin manifestations in humans. Leishmanial lesions are constituted of infected cells surrounded by macrophages interspersed with lymphocytes and polymorphonuclear cells (PMN). Since leukocyte infiltration is a common event of any inflammatory response, and monocytes are a major source of cytokines with chemotactic properties for PMN (IL-8) and for monocytes (MCAF), we asked whether L major might induce monocytes production of chemokines. Human monocytes were infected with L major ; supematants, that were collected after 18 hours of incubation, had chemotactic properties for monocytes as well as for PMN. Anti-MCAF Ig neutralized up to 52% of the monocyte chemotactic activity while anti-IL-8 neutralized up to 73% of the PMN chemotactic activity. Then we investigated whether chemokines expression by Le/shmama-infected-monocytes were accompanied with production of proinflammatory cytokines. TNF-o and IL-1II were detected at concentrations about 20 times lower than IL-8 in supematants derived from J.e/sftmama-infected monocytes while LPS was effective to the same extent to induce TNF-a, IL-1S and IL-8 secretion. These results suggest that L. major might induce a selective activation of monocytes for chemokines production to determine the recruitment of host cells permissive to the parasite
ELA2 genotype-phenotype correlation to be expected in patients with severe congenital neutropenia
No full textELA2 genotype-phenotype correlation to be expected in patients with severe congenital neutropeni
Primary immunodeficiencies appearing as combined lymphopenia, neutropenia, and monocytopenia.
No full textRecurrent or prolonged severe infections associated to panleukopenia strongly suggest primary immune disorders. In recent years, new immunodeficiency syndromes turned up: besides the importance of continuous clinical characterization throughout added reports, the phenotype can easily lead to diagnosis of known rare entities. Our purpose is to review main emerging genetic syndromes featuring lymphopenia combined to neutropenia and/or monocytopenia in order to facilitate diagnosis of rare primary immune deficiencies. (C) 2013 Elsevier B.V. All rights reserved
Novel and emerging treatments for Aicardi-Goutières syndrome
No full textIntroduction: Aicardi-Goutières syndrome (AGS) is the prototype of the type I interferonopathies, a new heterogeneous group of autoinflammatory disorders in which type I interferon plays a pivotal role. The disease usually manifests itself during infancy, primarily affecting the brain and the skin, and is characterized by cerebrospinal fluid chronic lymphocytosis and raised levels of interferon-alpha and by cardinal neuroradiological features: cerebral calcification, leukoencephalopathy and cerebral atrophy. Recently many aspects of the pathogenesis of AGS have been clarified, making it possible to hypothesize new therapeutic strategies. Areas covered: We here review recent data concerning pathogenesis and novel therapeutic strategies in AGS, including the use of Janus kinase inhibitors, reverse transcriptase inhibitors, anti-IFN-α antibodies, anti-interleukin antibodies, antimalarial drugs and other cGAS inhibitors. Expert opinion: Thanks to the identification of the molecular basis of AGS, many aspects of its pathogenesis have been clarified, making it possible to propose new therapeutic strategies for AGS and type I interferonopathies. A number of therapeutic options are now becoming possible, even though their efficacy is still to be proven. However, in spite of research advances coming from clinical trials and case series, there are still a number of open questions, which urgently need to be addressed
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