Microbial induction of inflammatory bowel disease associated gene TL1A (TNFSF15) in antigen presenting cells.
TL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Neutralizing anti-mouse TL1A Ab attenuates chronic colitis in two T-cell driven murine models, suggesting that TL1A is a central modulator of gut mucosal inflammation in inflammatory bowel disease. We showed previously that TL1A is induced by immune complexes via the Fc gamma R signaling pathway. In this study, we report that multiple bacteria, including gram negative organisms (E. coli, E. coli Nissle 1917, Salmonella typhimurium), gram positive organisms (Listeria monocytogenes, Staphylococcus epidermidis), partial anaerobes (Campylobacter jejuni), and obligate anaerobes (Bacteroides thetaiotaomicron, Bifidobacterium breve, Clostridium A4) activate TL1A expression in human APC, including monocytes and monocyte-derived DC. Bacterially induced TL1A mRNA expression correlates with the detection of TL1A protein levels. TL1A induced by bacteria is mediated in part by the TLR signaling pathway and inhibited by downstream blockade of p38 MAPK and NF-kappaB activation. Microbial induction of TL1A production by human APC potentiated CD4(+) T-cell effector function by augmenting IFN-gamma production. Our findings suggest a role for TL1A in pro-inflammatory APC-T cell interactions and implicate TL1A in host responses to enteric microorganisms.
Inflammatory Bowel Disease Center and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
David Q
DQ
Shih
Lola Y
LY
Kwan
Valerie
V
Chavez
Offer
O
Cohavy
Rivkah
R
Gonsky
Elmer Y
EY
Chang
Christopher
C
Chang
Charles O
CO
Elson
Stephan R
SR
Targan
D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology; D001419:Bacteria / Q000276:immunology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000276:immunology*
C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15