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- Dinarello, Charles, et al.
(författare)
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IL-1 family nomenclature
- 2010
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Ingår i: Nature Immunology. - : Nature Publishing Group. - 1529-2908 .- 1529-2916. ; 11:11, s. 973-973
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Oikonomou, Vasileios, et al.
(författare)
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The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.
- 2024
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Ingår i: The New England journal of medicine. - 1533-4406. ; 390:20, s. 1873-1884
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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| 5. |
- Wu, Cheng, 1985, et al.
(författare)
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Impacts of soil moisture on de novo monoterpene emissions from European beech, Holm oak, Scots pine, and Norway spruce
- 2015
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Ingår i: Biogeosciences. - 1726-4170 .- 1726-4189. ; 12, s. 177-191
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Tidskriftsartikel (refereegranskat)abstract
- Impacts of soil moisture on de novo monoterpene (MT) emissions from Holm oak, European beech, Scots pine, and Norway spruce were studied in laboratory experiments. The volumetric water content of the soil, Θ, was used as the reference quantity to parameterize the dependency of MT emissions on soil moisture and to characterize the severity of the drought. When θ dropped from 0.4m3 ×m-3 to ∼0.2m3 ×m-3 slight increases of de novo MT emissions were observed but with further progressing drought the emissions decreased to almost zero. In most cases the increases of MT emissions observed under conditions of mild drought were explainable by increases of leaf temperature due to lowered transpirational cooling. When Θ fell below certain thresholds, MT emissions decreased simultaneously with 2 and the relationship between Θ and MT emissions was approximately linear. The thresholds of θ (0.044-0.19m3 ×m-3) were determined, as well as other parameters required to describe the soil moisture dependence of de novo MT emissions for application in the Model of Emissions of Gases and Aerosols from Nature, MEGAN. A factorial approach was found appropriate to describe the impacts of 2, temperature, and light. Temperature and θ influenced the emissions largely independently from each other, and, in a similar manner, light intensity and θ acted independently on de novo MT emissions. The use of θ as the reference quantity in a factorial approach was tenable in predicting constitutive de novo MT emissions when θ changed on a time scale of days. Empirical parameterization with θ as a reference was only unsuccessful when soil moisture changed rapidly
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