The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity
Open accessAbstract
Lack of immunological tolerance against self-antigens results in autoimmune disorders. During onset of autoimmunity, dendritic cells (DCs) are thought to be critical for priming of self-reactive T cells that have escaped tolerance induction. However, because DCs can also induce T cell tolerance, it remains unclear whether DCs are required under steady-state conditions to prevent autoimmunity. To address this question, we crossed CD11c-Cre mice with mice that express diphtheria toxin A (DTA) under the control of a loxP-flanked neomycin resistance (neoR) cassette from the ROSA26 locus. Cre-mediated removal of the neoR cassette leads to DTA expression and constitutive loss of conventional DCs, plasmacytoid DCs, and Langerhans cells. These DC-depleted (ΔDC) mice showed increased frequencies of CD4 single-positive thymocytes and infiltration of CD4 T cells into peripheral tissues. They developed spontaneous autoimmunity characterized by reduced body weight, splenomegaly, autoantibody formation, neutrophilia, high numbers of Th1 and Th17 cells, and inflammatory bowel disease. Pathology could be induced by reconstitution of wild-type (WT) mice with bone marrow (BM) from ΔDC mice, whereas mixed BM chimeras that received BM from ΔDC and WT mice remained healthy. This demonstrates that DCs play an essential role to protect against fatal autoimmunity under steady-state conditions.
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Cites
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Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo
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Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
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TH-17 cells in the circle of immunity and autoimmunity
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Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase
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Cited by
Merad, M., Sathe, P., Helft, J., Miller, J., & Mortha, A. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074950 · Cited by 2,309
The microbiota regulates type 2 immunity through RORγt + T cells
Ohnmacht, C., Park, J.-H., Cording, S., Wing, J. B., Atarashi, K., Obata, Y., Gaboriau-Routhiau, V., Marques, R., Dulauroy, S., Fedoseeva, M., et al. (2015) · Science · doi:10.1126/science.aac4263 · Cited by 863
Self-citationEffective fiber hypertrophy in satellite cell-depleted skeletal muscle
McCarthy, J. J., Mula, J., Miyazaki, M., Erfani, R., Garrison, K., Farooqui, A. B., Srikuea, R., Lawson, B. A., Grimes, B., Keller, C., et al. (2011) · Development · doi:10.1242/dev.068858 · Cited by 616
Antigen presentation in the thymus for positive selection and central tolerance induction
Klein, L., Hinterberger, M., Wirnsberger, G., & Kyewski, B. (2009) · Nature Reviews Immunology · doi:10.1038/nri2669 · Cited by 571
The role of dendritic cells in autoimmunity
Ganguly, D., Haak, S., Sisirak, V., & Reizis, B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3477 · Cited by 507
Metadata
- Authors
- Ohnmacht, C., Pullner, A., King, S. B. S., Drexler, I., Meier, S., Brocker, T., & Voehringer, D.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-02-23
- Volume
- 206
- Issue
- 3
- Pages
- 549-559
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2124927041
- Cited by
- 578
- References
- 53
- FWCI
- 22.91
- Type
- journal article
- Language
- en
- Open access
- green
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- Ohnmacht, C., Pullner, A., King, S. B. S., Drexler, I., Meier, S., Brocker, T., & Voehringer, D. (2009). Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20082394
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