title: SUSTAINED TL1A(TNFSF15)EXPRESSION ON BOTH LYMPHOID AND MYELOID CELLS LEADS TO MILD SPONTANEOUS INTESTINAL INFLAMMATION AND FIBROSIS.
abstract: TL1A is a member of the TNF superfamily, and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, patients with certainTNFSF15variants over-express TL1A and have a higher risk of developing strictures in the small intestine. Consistently, mice with sustained Tl1a expression in either lymphoid or myeloid cells develop spontaneous ileitis and increased intestinal collagen deposition. Transgenic(Tg)mice with constitutive Tl1a expression in both lymphoid and myeloid cells were generated to assess theirin vivoconsequence. Constitutive expression of Tl1a in both lymphoid and myeloid cells showed increased spontaneous ileitis and collagen deposition than WT mice. T cells with constitutive expression of Tl1a in both lymphoid and myeloid cells were found to have a more activated phenotype, increased gut homing marker CCR9 expression, and enhanced Th1 and Th17 cytokine activity than WT mice. Although no differences in T cell activation marker, Th1 or Th17 cytokine activity, ileitis, or collagen deposition were found between constitutive Tl1a expression in lymphoid only, myeloid only, or combined lymphoid and myeloid cells. Double hemizygous Tl1a-Tg mice appeared to have worsened ileitis and intestinal fibrosis. Our findings confirm that TL1A-DR3 interaction is involved in T cell-dependent ileitis and fibrosis.
authors: F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA ; Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors: Libo
authors: L
authors: Zheng
authors: Xiaolan
authors: X
authors: Zhang
authors: Jeremy
authors: J
authors: Chen
authors: Ryan
authors: R
authors: Ichikawa
authors: Kori
authors: K
authors: Wallace
authors: Charalabos
authors: C
authors: Pothoulakis
authors: Hon Wai
authors: HW
authors: Koon
authors: Stephan R
authors: SR
authors: Targan
authors: David Q
authors: DQ
authors: Shih
keywords: fibrosis; ileitis; mucosal inflammation; transgenic
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