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 certain TNFSF15 variants 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 their in vivo consequence. 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.

Journal

Journal ID (publisher-id): 1886

Journal ID (MPID): 122234

Title: European Journal of Microbiology and Immunology

Abbreviated Title: EuJMI

Publisher: Akadémiai Kiadó, co-published with Springer Science+Business Media B.V., Formerly Kluwer Academic Publishers B.V.

ISSN (Print): 2062-509X

ISSN (Electronic): 2062-8633

Publication date (Print): 1 March 2013

Volume: 3

Issue: 1

Pages: 11-20

Affiliations

[ ¹ ] F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

[ ² ] Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China

[ ³ ] Center for Inflammatory Bowel Diseases, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA

[ ⁴ ] F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, 8700 Beverly Blvd., Suite 4065, Los Angeles, CA, 90048, USA

Author notes

[* ] [phone], targans@ 123456cshs.org

[** ] [phone], david.shih@ 123456csmc.edu

Article

Other ID: 2

DOI: 10.1556/EuJMI.3.2013.1.2

PMC ID: 3638202

PubMed ID: 23638306

Product

Self URI (journal page): https://akademiai.com/info/collections/scienceopen/life