TY - JOUR
T1 - TL1A/TNFSF15 directly induces proinflammatory cytokines, including TNFα, from CD3+CD161+ T cells to exacerbate gut inflammation
AU - Jin, S.
AU - Chin, J.
AU - Seeber, S.
AU - Niewoehner, J.
AU - Weiser, B.
AU - Beaucamp, N.
AU - Woods, J.
AU - Murphy, C.
AU - Fanning, A.
AU - Shanahan, F.
AU - Nally, K.
AU - Kajekar, R.
AU - Salas, A.
AU - Planell, N.
AU - Lozano, J.
AU - Panes, J.
AU - Parmar, H.
AU - Demartino, J.
AU - Narula, S.
AU - Thomas-Karyat, D. A.
PY - 2013/9
Y1 - 2013/9
N2 - Tumor necrosis factor (TNF)-like cytokine 1A (TL1A)/TNF superfamily member 15 (TNFSF15) is a proinflammatory cytokine and TNFα superfamily member that is linked preclinically and clinically to inflammatory bowel disease (IBD). By homology and function, TNFα is its closest family member. In this study, we investigated the mechanism of TL1A-induced inflammation in CD4+ T cells and compared it with the TNFα pathway. We found that TL1A induces proinflammatory cytokines, including TNFα, from isolated human CD4+CD161+ T cells, whereas these cells were resistant to TNFα treatment. Anti-TNFα failed to block TL1A-induced cytokine production, indicating that the effects of TL1A are direct. Lastly, CD161 and TL1A expression were significantly and selectively increased in gut tissue biopsies, but not in the peripheral blood, from IBD patients. Thus, TLIA not only functions upstream of TNFα, driving its expression from CD161+ T cells, but is also independent of TNFα. These findings may have therapeutic IBD implications.
AB - Tumor necrosis factor (TNF)-like cytokine 1A (TL1A)/TNF superfamily member 15 (TNFSF15) is a proinflammatory cytokine and TNFα superfamily member that is linked preclinically and clinically to inflammatory bowel disease (IBD). By homology and function, TNFα is its closest family member. In this study, we investigated the mechanism of TL1A-induced inflammation in CD4+ T cells and compared it with the TNFα pathway. We found that TL1A induces proinflammatory cytokines, including TNFα, from isolated human CD4+CD161+ T cells, whereas these cells were resistant to TNFα treatment. Anti-TNFα failed to block TL1A-induced cytokine production, indicating that the effects of TL1A are direct. Lastly, CD161 and TL1A expression were significantly and selectively increased in gut tissue biopsies, but not in the peripheral blood, from IBD patients. Thus, TLIA not only functions upstream of TNFα, driving its expression from CD161+ T cells, but is also independent of TNFα. These findings may have therapeutic IBD implications.
UR - https://www.scopus.com/pages/publications/84883182349
U2 - 10.1038/mi.2012.124
DO - 10.1038/mi.2012.124
M3 - Article
C2 - 23250276
AN - SCOPUS:84883182349
SN - 1933-0219
VL - 6
SP - 886
EP - 899
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 5
ER -
