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Regulation of autoimmune germinal center reactions in lupus-prone BXD2 mice by follicular helper T cells
- Source :
- PLoS ONE, Vol 10, Iss 3, p e0120294 (2015), PLoS ONE, PLOS ONE(10): 3
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis, offering a useful animal model to study autoimmune lupus. Although initial studies showed a critical contribution of IL-17 and Th17 cells in mediating autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh) cells remains incompletely understood. We found that both the frequency of Th17 cells and the levels of IL-17 in circulation in BXD2 mice were comparable to those of wild-type. By contrast, the frequency of PD-1(+)CXCR5(+) Tfh cells was significantly increased in BXD2 mice compared with wild-type mice, while the frequency of PD-1(+)CXCR5(+)Foxp3(+) follicular regulatory T (Tfr) cells was reduced in the former group. The frequency of Tfh cells rather than that of Th17 cells was positively correlated with the frequency of germinal center B cells as well as the levels of autoantibodies to dsDNA. More importantly, CXCR5(+) CD4(+) T cells isolated from BXD2 mice induced the production of IgG from naive B cells in an IL-21-dependent manner, while CCR6(+) CD4(+) T cells failed to do so. These results together demonstrate that Tfh cells rather than Th17 cells contribute to the autoimmune germinal center reactions in BXD2 mice.
- Subjects :
- CD4-Positive T-Lymphocytes
Receptors, CXCR5
Science
Naive B cell
Autoimmunity
03 medical and health sciences
Interleukin 21
Mice
0302 clinical medicine
medicine
Animals
Lupus Erythematosus, Systemic
B cell
030304 developmental biology
Autoantibodies
0303 health sciences
Multidisciplinary
CD40
Systemic lupus erythematosus
biology
Interleukins
FOXP3
Germinal center
T-Lymphocytes, Helper-Inducer
medicine.disease
Germinal Center
medicine.anatomical_structure
Immunoglobulin G
Immunology
biology.protein
Interleukin 12
Th17 Cells
Medicine
Disease Susceptibility
030215 immunology
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....05ea2271316979f7c0089f45807b3d01