Toll-like receptor 6 stimulation promotes T-helper 1 and 17 responses in gastrointestinal-associated lymphoid tissue and modulates murine experimental colitis
| Autor: | Morgan, M E, Koelink, P J, Zheng, B, den Brok, M H M G M, van de Kant, H J G, Verspaget, H W, Folkerts, G, Adema, G J, Kraneveld, A D, Sub General Pharmacology, Sub Developmental Biology, Sub Airway in vivo Pharmacology, Sub Immunopharmacology, Pharmacology |
|---|---|
| Přispěvatelé: | Sub General Pharmacology, Sub Developmental Biology, Sub Airway in vivo Pharmacology, Sub Immunopharmacology, Pharmacology |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Lymphoid Tissue
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Immunology Fluorescent Antibody Technique Spleen Biology Inflammatory bowel disease Peripheral blood mononuclear cell Article Mice RAR-related orphan receptor gamma medicine Animals Humans Immunology and Allergy Colitis Cells Cultured Mice Inbred BALB C Toll-like receptor FOXP3 Th1 Cells medicine.disease Gastrointestinal Tract Disease Models Animal TLR2 Toll-Like Receptor 6 medicine.anatomical_structure Gene Expression Regulation Th17 Cells Female Transcription Factors |
| Zdroj: | Mucosal Immunology, 7(5), 1266-1277 Mucosal Immunology Mucosal Immunology, 7, 1266-77 Mucosal Immunology, 7, 5, pp. 1266-77 Mucosal Immunology, 7(5), 1266. Nature Publishing Group |
| ISSN: | 1933-0219 |
| Popis: | Item does not contain fulltext T-helper 1 and 17 (Th1/Th17) responses are important in inflammatory bowel disease (IBD), and research indicates that Toll-like receptor 6 (TLR6) stimulation leads to Th17 cell development within the lung. The gastrointestinal tract, like the lung, is a mucosal surface that is exposed to bacterially derived TLR6 ligands. Thus, we looked at the effects of TLR6 stimulation on the expression of Th17-, Th1-, and regulatory T-cell-associated transcription factors; RORgammat, T-bet, and Foxp3, respectively; in CD4+ T cells within gut-associated lymphoid tissue (GALT) in vitro and in vivo. Cells from GALT and spleen were stimulated with anti-CD3 and TLR ligands for TLR1/2 and TLR2/6 (Pam3CSK4 and FSL-1, respectively). FSL-1 was more effective than Pam3CSK4 at inducing Th1 and Th17 responses in the GALT while Pam3CSK4 rivaled FSL-1 in the spleen. TLR6 was further explored in vivo using experimental colitis. Tlr6-/- mice were resistant to colitis, and oral FSL-1 led to more severe colitis in wild-type mice. Similar pro-inflammatory reactions were seen in human peripheral blood mononuclear cells, and TLR6 expression was directly correlated with RORC mRNA levels in inflamed intestines of IBD patients. These results demonstrate that TLR6 supports Th1- and Th17-skewed responses in the GALT and might be an important target for the development of new medical interventions in IBD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|