Reference - Detail
| RRC ID | 67206 |
|---|---|
| Author | Serr I, Fürst RW, Achenbach P, Scherm MG, Gökmen F, Haupt F, Sedlmeier EM, Knopff A, Shultz L, Willis RA, Ziegler AG, Daniel C. |
| Title | Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice. |
| Journal | Nat Commun |
| Abstract |
Immune tolerance is executed partly by Foxp3(+)regulatory T (Treg) cells, which suppress autoreactive T cells. In autoimmune type 1 diabetes (T1D) impaired tolerance promotes destruction of insulin-producing β-cells. The development of autoantigen-specific vaccination strategies for Foxp3(+)Treg-induction and prevention of islet autoimmunity in patients is still in its infancy. Here, using human haematopoietic stem cell-engrafted NSG-HLA-DQ8 transgenic mice, we provide direct evidence for human autoantigen-specific Foxp3(+)Treg-induction in vivo. We identify HLA-DQ8-restricted insulin-specific CD4(+)T cells and demonstrate efficient human insulin-specific Foxp3(+)Treg-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. Induced human Tregs are stable, show increased expression of Treg signature genes such as Foxp3, CTLA4, IL-2Rα and TIGIT and can efficiently suppress effector T cells. Such Foxp3(+)Treg-induction does not trigger any effector T cells. These T1D vaccine candidates could therefore represent an expedient improvement in the challenge to induce human Foxp3(+)Tregs and to develop novel precision medicines for prevention of islet autoimmunity in children at risk of T1D. |
| Volume | 7 |
| Pages | 10991 |
| Published | 2016-3-15 |
| DOI | 10.1038/ncomms10991 |
| PII | ncomms10991 |
| PMID | 26975663 |
| PMC | PMC4796321 |
| MeSH | Adolescent Adult Animals Autoantigens / immunology Autoimmunity / immunology CTLA-4 Antigen / genetics CTLA-4 Antigen / immunology Child Child, Preschool Diabetes Mellitus, Type 1 / drug therapy Diabetes Mellitus, Type 1 / immunology* Female Forkhead Transcription Factors / genetics Forkhead Transcription Factors / immunology* Gene Expression Regulation / immunology* HLA-DQ Antigens / genetics Hematopoietic Stem Cell Transplantation Humans Immune Tolerance / immunology Insulin / immunology* Interleukin-2 Receptor alpha Subunit / genetics Interleukin-2 Receptor alpha Subunit / immunology Lymphocyte Activation / immunology* Male Mice Mice, Transgenic Receptors, Immunologic / genetics Receptors, Immunologic / immunology Self Tolerance / immunology* T-Lymphocytes, Regulatory / immunology* Vaccines / immunology* Young Adult |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 35 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Human and Animal Cells | HEV0110 |