TL1A produced by lamina propria macrophages induces Th1 and Th17 immune responses in cooperation with IL-23 in patients with Crohn's disease.
BACKGROUND
Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily and contributes to the pathogenesis of Crohn's disease (CD) by stimulating T-helper (Th) 1 cells. In addition to Th1, recent studies have focused on the role of Th17 cells in the pathogenesis of CD. Here we tried to clarify the role of TL1A in Th1 and Th17 immunity in CD.


METHODS
TL1A expression was assessed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) in lamina propria (LP) macrophages (LP-M phi s) from normal controls (NC) and patients with CD or ulcerative colitis (UC). Purified LP CD4(+) T cells were stimulated with TL1A and/or IL-23 and interferon gamma (IFN-gamma) and interleukin (IL)-17 levels were analyzed. We also examined the effect of TL1A on naïve CD4(+) T-cell differentiation.


RESULTS
We found that LP-M phi s are a major producer of TL1A. TL1A expression was markedly enhanced in LP-M phi s from CD patients compared with NC or UC patients. IL-23, in addition to TL1A, was induced in LP-M phi s by commensal bacteria stimulation. TL1A and IL-23 synergistically promoted the production of IFN-gamma and IL-17 by LP T cells, while TL1A alone did not induce cytokine production. Furthermore, TL1A promoted Th17 differentiation from naïve T cells by LP-M phi s; however, IL-23 did not show any synergistic effects on Th17 differentiation.


CONCLUSIONS
TL1A expressed in LP-M phi s might play an important role in the pathogenesis of CD by inducing Th1 and Th17 immunity. IL-23 differentially regulated these functions of TL1A on memory and naïve T cells.
Kamada
Nobuhiko
N
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hisamatsu
Tadakazu
T
Honda
Haruki
H
Kobayashi
Taku
T
Chinen
Hiroshi
H
Takayama
Tetsuro
T
Kitazume
Mina T
MT
Okamoto
Susumu
S
Koganei
Kazutaka
K
Sugita
Akira
A
Kanai
Takanori
T
Hibi
Toshifumi
T
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000502:physiology*
D020381:Interleukin-17; D053759:Interleukin-23; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15