TL1A increased the differentiation of peripheral Th17 in rheumatoid arthritis.
The interaction between TNF-like protein 1A (TL1A) and its receptors, death receptor-3 (DR3) may be involved in the pathogenesis of rheumatoid arthritis (RA) through the regulation of Th17. Our data here showed that TL1A could significantly promote Th17 differentiation and RORc mRNA expression from naive T cells and enhance IL-17A level in cell supernatant in RA patients. Anti-TNF-α treatment had suppressive effects on TL1A-mediated Th17 differentiation and RORc mRNA expression. In addition, The percentage of peripheral CD4+DR3+T cells of RA was significantly higher than that of healthy controls (HC), and this increased percentage of CD4+DR3+T cells was obviously up-regulated when stimulated with anti-CD3 and anti-CD28 antibody in RA patients. However, anti-CD3 and anti-CD28 antibody stimulation did not increase the percentage of CD4+DR3+IL-17A+T cells in RA patients. These results suggested that TL1A could promote Th17 differentiation in RA via the activation of RORc, and this effect may be mediated by the binding of TL1A with DR3.
Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, PR China.
Min
M
Zhou
Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, PR China.
Rui
R
Liu
Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, PR China.
Dinglei
D
Su
Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, PR China.
Xuebing
X
Feng
Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, PR China; Department of Immunology, College of Medical Basic Science, Dalian Medical University, Dalian, Liaoning 116044, PR China. Electronic address: lixia416@163.com.
Xia
X
Li
D000906:Antibodies / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; C508717:IL17A protein, human; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; C539900:RORC protein, human; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha
Death receptor 3 (DR3); RORc; Rheumatoid arthritis; TNF-like cytokine 1A (TL1A); Th17