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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Miele, Lucio Prabhakar, Bellur S. Bruno, Joseph C. Vasu, Chenthamarakshan Bhattacharya, Palash Gopisetty, Anupama Haddad, Christine |
| Description | Country affiliation: United States Author Affiliation: Gopisetty A ( Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA.) |
| Abstract | Earlier, we had demonstrated that treatment with low dose of GM-CSF can prevent the development of experimental autoimmune thyroiditis (EAT), experimental autoimmune myasthenia gravis, and type 1 diabetes, and could also reverse ongoing EAT and experimental autoimmune myasthenia gravis. The protective effect was mediated through the induction of tolerogenic CD11C(+)CD8 (-) dendritic cells (DCs) and consequent expansion of Foxp3(+) regulatory T cells (Tregs). Subsequently, we showed that GM-CSF acted specifically on bone marrow precursors and facilitated their differentiation into tolerogenic dendritic cells (DCs; GM-CSF-induced bone marrow-derived DCs [GM-BMDCs]), which directed Treg expansion in a contact-dependent manner. This novel mechanism of Treg expansion was independent of TCR-mediated signaling but required exogenous IL-2 and cosignaling from DC-bound OX40L. In this study, we observed that OX40L-mediated signaling by GM-BMDCs, although necessary, was not sufficient for Treg expansion and required signaling by Jagged1. Concurrent signaling induced by OX40L and Jagged1 via OX40 and Notch3 receptors expressed on Tregs was essential for the Treg expansion with sustained FoxP3 expression. Adoptive transfer of only OX40L(+)Jagged1(+) BMDCs led to Treg expansion, increased production of IL-4 and IL-10, and suppression of EAT in the recipient mice. These results showed a critical role for OX40L- and Jagged1-induced cosignaling in GM-BMDC-induced Treg expansion. |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1202298 |
| Journal | The Journal of Immunology |
| Issue Number | 11 |
| Volume Number | 190 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2013-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium-binding Proteins Metabolism Dendritic Cells Intercellular Signaling Peptides And Proteins Membrane Proteins Ox40 Ligand Signal Transduction T-lymphocytes, Regulatory Cytology Immunology Animals B7 Antigens Bone Marrow Cells Drug Effects Cell Membrane Disease Models, Animal Forkhead Transcription Factors Granulocyte-macrophage Colony-stimulating Factor Pharmacology Ligands Lymphocyte Activation Mice Receptors, Notch Thyroiditis, Autoimmune Research Support, N.i.h., Extramural Discipline Immunology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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