کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6119227 | 1592294 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Altered subcellular localization of IL-33 leads to non-resolving lethal inflammation
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کلمات کلیدی
NeoRFCMIL-33FRCHEVSCsEosinophilia - ائوزینوفیلیاEosinophils - ائوزینوفیلهاImmunohistochemistry - ایمونوهیستوشیمیIHC - ایمونوهیستوشیمیInterleukin-33 - اینترلوکین 33fibroblastic reticular cell - سلول مجزا فیبروبلاستیEOs - عناوینFlow cytometry - فلوسیتومتریKnock-in mouse - ماوس را بکشMacrophage - ماکروفاژ Alveolar macrophages - ماکروفاژهای آلوئولارbone marrow - مغز استخوانMAC - مکwild type - نوع وحشیImmune homeostasis - هوموستاز ایمنhigh endothelial venule - ونول اندوتلیوم بالاLymph node - گره های لنفاوی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Non-resolving inflammation is a major contributor to chronic disease pathogenesis, including that of cancer, chronic obstructive pulmonary disease, asthma, arthritis, inflammatory bowel disease, multiple sclerosis and obesity. Some cytokines, such as IL-1α and IL-33, may act as endogenous alarmins that contribute to non-resolving inflammation. These cytokines are constitutively expressed in the nucleus and are thought to promote inflammation only upon release during tissue damage or cell necrosis. However, the importance of their nuclear localization in immune homeostasis is not fully understood. We describe herein a novel mouse model in which the nuclear localization signal of IL-33 is abolished and demonstrate for the first time that, alone, altered subcellular localization of IL-33 dramatically affects immune homeostasis. Heterozygous IL33tm1/+ mice display elevated serum IL-33 levels, indicating that IL-33 is constitutively released when not actively targeted to the nucleus. IL33tm1/+ mice succumb to lethal inflammation characterized by eosinophil-dominated immune cell infiltration of multiple organs. The profound inflammatory phenotype is dependent on mediators downstream of ST2 as ST2-null mice are protected in spite of high serum IL-33 levels. Importantly, IL-33 transcript levels in this knock-in mouse model remain under endogenous control. We adopt the term “nuclear alarmin” to describe a danger signal that is primarily regulated by nuclear compartmentalization in this fashion.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Autoimmunity - Volume 55, December 2014, Pages 33-41
Journal: Journal of Autoimmunity - Volume 55, December 2014, Pages 33-41
نویسندگان
Juliana Bessa, Claas Aiko Meyer, Maria Cristina de Vera Mudry, Sonja Schlicht, Susan H. Smith, Antonio Iglesias, Javier Cote-Sierra,