TSLP: a novel potent proinflammatory mediator that activates myeloid dendritic cells to stimulate Th1 and Th17 activity in rheumatoid arthritis
| Autor: | Joel A G van Roon, Kim M G van der Wurff-Jacobs, Floris P J G Lafeber, C. Erik Hack, Frederique M Moret |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Chemokine
Thymic stromal lymphopoietin biology business.industry medicine.medical_treatment T cell Immunology Interleukin Inflammation General Biochemistry Genetics and Molecular Biology T cell cytokine production Proinflammatory cytokine Cytokine medicine.anatomical_structure Rheumatology medicine biology.protein Immunology and Allergy medicine.symptom business |
| Zdroj: | Annals of the Rheumatic Diseases. 70:A43-A44 |
| ISSN: | 0003-4967 |
| DOI: | 10.1136/ard.2010.148981.4 |
| Popis: | Background Thymic stromal lymphopoietin (TSLP) is well known for its potent activation of myeloid dendritic cells (mDCs) resulting in Th2-mediated immune responses. TSLP signals cells via the interleukin (IL)-7 receptor-α chain (IL-7Rα), shared with IL-7, together with the TSLP receptor (TSLPR) subunit. Recently, the authors have demonstrated that prevention of TSLPR signalling strongly reduces Th17-driven experimental arthritis and immunopathology. Furthermore, the authors have shown that administration of TSLP enhances severity of inflammation and joint destruction in collagen induced arthritis. Objective To determine the levels of TSLP and TSLPR in joints of rheumatoid arthritis (RA) patients and the capacity of TSLP to induce mDC-dependent T cell activation. Methods TSLP was measured in synovial fluid (SF) of RA (n=44) and osteoarthritis (OA) patients (n=20). CD1c + mDC numbers and TSLPR expression on these cells were assessed by FACS analysis in paired samples of SF and peripheral blood (PB) from RA patients (n=7). mDCs, isolated from PB of RA patients (n=10) were stimulated with TSLP for 24 h and cytokine production was measured. Washed TSLP-activated mDCs were added to autologous CD4 T cells from PB in the absence of additional stimuli, cultured for 6 days and subsequently proliferation was measured. T cell cytokine production was measured upon restimulation with ionomycin/PMA. Results TSLP levels in SF of RA patients were increased compared to OA patients (460 vs 75 pg/ml, respectively, p + mDC numbers from SF were increased compared to PB (3.8% vs 0.7%, respectively, p TSLP significantly stimulated production of chemokines TARC and MIP1α by mDCs (TARC; from 4 to 89, MIP1α; from 1545 to 6293 pg/ml, p Conclusion The authors9 data indicate that increased intra-articular TSLP concentrations in RA potently activate TSLPR-expressing mDCs from RA patients to cause chemotaxis and activation of arthritogenic T cells. This suggests that TSLP and its receptor are novel therapeutic targets for RA. |
| Databáze: | OpenAIRE |
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