title: TL1A as a Potential Local Inducer of IL17A Expression in Colon Mucosa of Inflammatory Bowel Disease Patients.
abstract: Interaction between TL1A and death receptor 3 (DR3) co-stimulates T cells, induces production of several pro-inflammatory cytokines and has been linked to pathogenesis of inflammatory bowel disease (IBD). This study aimed to establish a link between expression of TL1A and selected TL1A-induced pro-inflammatory cytokines involved in IBD pathogenesis (IL-4, IL-13, IL-17A and IFN-γ) and to investigate a connection between serum concentration of TL1A in patients with IBD and activation of peripheral blood T cells. Elevated levels of IL-4 (2.91-fold) and IL-13 (4.05-fold) mRNA were detected in the inflamed colon mucosa of patients with ulcerative colitis (UC), IFN-γ mRNA was upregulated (3.23-fold) in the inflamed colon mucosa of patients with Crohn's disease (CD), whereas upregulation of IL-17A and TL1A mRNA was present in the inflamed colon mucosa of patients with both CD and UC (IL-17A: 4.48-fold and 2.74-fold, TL1A: 3.19-fold and 3.22-fold, respectively) vs. control subjects. We did not detect any changes in DR3 mRNA expression in the investigated groups of patients. TL1A mRNA level in colon mucosa of patients with IBD correlated only with the level of IL-17A mRNA but no other investigated cytokines. In colon mucosa, expression of TL1A and DR3 was localized to enterocytes and lamina propria mononuclear cells. We did not find any correlation between serum concentrations of TL1A and IL-17A or changes of CD4(+) or CD8(+) lymphocytes phenotype in patients with IBD. Therefore, our data indicate that TL1A may contribute to pathogenesis of IBD via local but not systemic induction of IL-17A but not IL-4, IL-13 or IFN-γ.
authors.affiliation: Department of Histology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: T J
authors.initials: TJ
authors.lastname: Ślebioda
authors.affiliation: Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Bojarska-Junak
authors.affiliation: Department of Histology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Stanisławowski
authors.affiliation: Department of Histology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Cyman
authors.affiliation: Department of Histology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: P M
authors.initials: PM
authors.lastname: Wierzbicki
authors.affiliation: Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Roliński
authors.affiliation: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Celiński
authors.affiliation: Department of Histology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Kmieć
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics / Q000378:metabolism; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C508717:IL17A protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; D020381:Interleukin-17; D012333:RNA, Messenger; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D015847:Interleukin-4; D007371:Interferon-gamma