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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Miaw, Shi-Chuen Yu, Jhang-Sian Wu, Sheng-Yang Liu, Fu-Tong Wu-Hsieh, Betty A. |
| Description | Country affiliation: Taiwan Author Affiliation: Wu SY ( Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei 10051, Taiwan.) |
| Abstract | Galectin-3 (gal3) is known for its immunoregulatory functions in infectious, autoimmune, and inflammatory diseases. However, little is known about its regulatory role in the host's IL-17A response to infection. Using a mouse model of histoplasmosis in which both Th1 and Th17 responses contribute to fungal clearance, we investigated how gal3 regulates IL-17A responses. Our study showed that Histoplasma infection induced gal3(-/-) dendritic cells to produce significantly higher levels of IL-23, TGF-ß1, and IL-1ß than did gal3(+/+) cells. Infected by the same inoculum of Histoplasma, gal3(-/-) mice had lower fungal burden and produced higher levels of IL-23/IL-17-axis cytokines and lower levels of IL-12 and IFN-γ. Additionally, there was an increase in Th17 cells and a reduction in Th1 cells in infected gal3(-/-) mice. In vitro Th1/Th17-skewing experiments excluded the intrinsic effect of gal3 on Th cell differentiation. Although neutrophils from both gal3(+/+) and gal3(-/-) mice produced IL-17A upon IL-23 stimulation, their contribution to IL-17A production was greater in gal3(-/-) mice than in gal3(+/+) mice. Compared with gal3(+/+) dendritic cells, adoptive transfer of gal3(-/-) dendritic cells resulted in production of significantly higher levels of IL-17-axis cytokines and reduced fungal burden. It appears that reduced fungal burden and preferential IL-17A response in gal3(-/-) mice by both Th17 cells and neutrophils were the result of preferential production of IL-23/IL-17-axis cytokines by dendritic cells. Our study showed that gal3 negatively regulates IL-17A responses through inhibition of IL-23/IL-17-axis cytokine production by dendritic cells. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| Journal | The Journal of Immunology |
| Issue Number | 7 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cytokines Biosynthesis Dendritic Cells Immunology Metabolism Galectin 3 Histoplasma Histoplasmosis Animals Cell Differentiation Genetics Host-pathogen Interactions Interleukin-17 Pharmacology Interleukin-23 Macrophage Activation Macrophages Microbiology Mice Mice, Knockout Neutrophils Th17 Cells Cytology Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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