| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Boon, Louis Read, Simon Ross, Ellen M. Gleeson, Paul A. Van Driel, Ian R. Allen, Stacey Houghton, Fiona J. Bourges, Dorothée Bedoui, Sammy |
| Description |
Author Affiliation: Bourges D ( Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Ross EM ( Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Allen S ( Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Read S ( Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Houghton FJ ( Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); Bedoui S ( Department of Microbiology and Immunology, Peter Doherty Institute for Immunology and Infection, The University of Melbourne, Parkville, Victoria 3010, Australia); Boon L ( Bioceros Holding BV, 3584 CM Utrecht, The Netherlands.); Gleeson PA ( Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia); van Driel IR ( Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia) |
| Abstract |
It has been proposed that activation of dendritic cells (DCs) presenting self-antigens during inflammation may lead to activation of autoreactive T cells and the development of autoimmunity. To test this hypothesis, we examined the presentation of the autoantigen recognized in autoimmune gastritis, gastric H(+)/K(+) ATPase, which is naturally expressed in the stomach and is constitutively presented in the stomach-draining lymph nodes. Systemic administration to mice of the TLR9 agonist CpG DNA, agonist anti-CD40 Ab, or TLR4 agonist LPS all failed to abrogate the process of peripheral clonal deletion of H(+)/K(+) ATPase-specific CD4 T cells or promote the development of autoimmune gastritis. We demonstrated that migratory DCs from the stomach-draining lymph nodes are the only DC subset capable of constitutively presenting the endogenous gastric H(+)/K(+) ATPase autoantigen in its normal physiological context. Analysis of costimulatory molecules indicated that, relative to resident DCs, migratory DCs displayed a partially activated phenotype in the steady state. Furthermore, migratory DCs were refractory to stimulation by transient exposure to TLR agonists, as they failed to upregulate costimulatory molecules, secrete significant amounts of inflammatory cytokines, or induce differentiation of effector T cells. Together, these data show that transient systemic inflammation failed to break tolerance to the gastric autoantigen, as migratory DCs presenting the gastric autoantigen remain tolerogenic under such conditions, demonstrating the robust nature of peripheral tolerance. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
11 |
| Volume Number |
192 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-06-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Autoantigens Immunology Cell Movement Dendritic Cells Immune Tolerance Stomach Adjuvants, Immunologic Adverse Effects Pharmacology Animals Genetics Drug Effects Pathology Inflammation Chemically Induced Mice Mice, Inbred Balb C Mice, Knockout Oligodeoxyribonucleotides Toll-like Receptor 9 Agonists Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
