TY  - EJOU
AU  - Al-Azab, Mahmoud 
AU  - Wei, Jing 
AU  - Ouyang, Xunli 
AU  - Elkhider, Abdalkhalig 
AU  - Walana, Williams 
AU  - Sun, Xiaotong 
AU  - Tang, Yawei 
AU  - Wang, Bing 
AU  - Li, Xia 

TI  - TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis
T2  - European Cytokine Network

PY  - 2018
VL  - 29
IS  - 1
SN  - 1952-4005

AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation.
One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the
local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine
1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior
through TNF receptor 2 (TNFR2). We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration
using patients’ samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in
chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue
Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RAFLS
promoted significantly IHH protein expression. However, both mRNA and protein levels decreased substantially
after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation
of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that
TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.
KW  - rheumatoid arthritis
KW  -  TNF-like cytokine 1A
KW  -  fibroblast-like synoviocytes
KW  -  Indian hedgehog
KW  -  patched1
KW  -  2 receptors
KW  -  TNF-receptor2

DO  - 10.1684/ecn.2018.0405