دورية أكاديمية
A6.9 Distinct expression of T-cell homing molecules in human autoimmune lymph node stromal cells upon TLR-3 triggering
| العنوان: | A6.9 Distinct expression of T-cell homing molecules in human autoimmune lymph node stromal cells upon TLR-3 triggering |
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| المؤلفون: | Hähnlein, J, Ramwadhdoebe, TH, Semmelink, JF, Choi, IY, Smits, NAM, Berger, FH, Maas, M, Gerlag, DM, Geijtenbeek, TBH, Tak, PP, van Baarsen, LBM |
| بيانات النشر: | BMJ Publishing Group Ltd |
| سنة النشر: | 2015 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | 6. Molecular regulation, angiogenesis |
| الوصف: | Background Rheumatoid arthritis (RA) is a prototypic autoimmune disease in which systemic autoimmunity precedes overt synovial tissue inflammation. The aetiology of RA is still unknown and systemic autoimmunity is probably initiated by an unidentified mechanism outside the synovium. Adaptive immune responses are generated in lymphoid tissue where the stromal compartment plays a crucial role in regulating T- and B-cell function. Murine studies have demonstrated that exposure to viral products can alter the interaction between lymph node stromal cells (LNSCs) and T-cells. However, little is known about the ability of human LNSCs to sense pathogens and their response to viral products. Viral infections have also been implicated the initiation and promotion of autoimmunity. Objective Here we investigated which Toll-like receptors (TLRs) human LNSCs express and how TLR-3 triggering by polyI:C, affects gene and protein expression of human LNSC derived from lymph nodes obtained of healthy individuals and individuals with evidence of autoimmunity. Material and methods We included individuals with arthralgia who were positive for IgM rheumatoid factor and/or anti-citrullinated protein (n = 10; RA risk group), RA patients (n = 12) and healthy controls (HCs, n = 10). All subjects underwent ultrasound-guided inguinal lymph node biopsy and LNSCs were cultured directly from freshly collected biopsies. LNSCs of passage 3–6 were stimulated with polyI:C after which mRNA and protein levels were measured by qPCR, flow cytometry or ELISA. Results Cultured human LNSCs expressed TLR1 to 9 with exception of TLR-8 mRNA and the strongest expression was observed for TLR-3. TLR-3 triggering in human LNSCs induced expression of adhesion molecules like VCAM-1 and ICAM-1 and inflammatory cytokines such as IL-6. In addition TLR-3 itself and type I IFN stimulated genes (ISGs) like IRF-7 and IP-10 were upregulated in response to polyI:C. For the ISG MxA we observed a significant lower induction in RA risk individuals compared with HCs (p = ... |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| العلاقة: | http://ard.bmj.com/cgi/content/short/74/Suppl_1/A58-cTest; http://dx.doi.org/10.1136/annrheumdis-2015-207259.135Test |
| DOI: | 10.1136/annrheumdis-2015-207259.135 |
| الإتاحة: | https://doi.org/10.1136/annrheumdis-2015-207259.135Test http://ard.bmj.com/cgi/content/short/74/Suppl_1/A58-cTest |
| حقوق: | Copyright (C) 2015, BMJ Publishing Group Ltd |
| رقم الانضمام: | edsbas.5920B149 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/annrheumdis-2015-207259.135 |
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