Defining the immune regulatory function of LIGHT specific LTβR interactions in mucosal tissue. (MUC5P.747)
| Autor: | Sonja Zahner, Petra Krause, Gisen Kim, Venetia Morris, Alexei Tumanov, Yang Fu, Mitchell Kronenberg |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 194:138.5-138.5 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.194.supp.138.5 |
| Popis: | Inflammatory bowel disease is characterized by an exacerbated inflammation of the intestine. While blocking tumor necrosis factor α (TNFα) helps many patients, it also causes significant side effects including a hampered host defense. TNFSF14/LIGHT, another member of the TNF superfamily, can bind to two receptors, HVEM and lymphotoxin β receptor (LTβR). Though LIGHT expression by T cells has been described to be inflammatory, we have recently shown that LIGHT interaction with LTβR is protective in murine colitis, indicating therapeutic promise for LIGHT. In absence of LIGHT-LTβR interactions, the innate immune system prolongs and exacerbates intestinal inflammation, with increased IL-1β and oncostatin M expression leading to increased IL-6. To define the cell-cell interactions leading to the excessive inflammation, we have analyzed mice with a conditional deletion of the LTβR. A dendritic cell-specific lack of the LTβR caused aggravated colitis compared to wild type but less severe colitis than in LIGHT-deficient mice. Thus, other LTβR-expressing cell types may be involved. To identify the cell types involved in the protective LIGHT-LTβR interaction in mouse colitis, we generated conditional mutants of LIGHT and are currently analyzing these mice. Intriguingly, mice lacking lymphotoxin β (LTβ), a subunit of the other ligand for the LTβR, were protected from severe disease. These data suggest that there are antagonistic effects of LIGHT and LTβ engagement of the LTβR. |
| Databáze: | OpenAIRE |
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