Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific
Many experimental therapies for autoimmune diseases, such as multiple sclerosis (MS), aim to bias T cells toward tolerogenic phenotypes without broad suppression. However, the link between local signal integration in lymph nodes (LNs) and the specificity of systemic tolerance is not well understood....
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| Format: | Article |
| Language: | English |
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Elsevier
2016-09-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471631097X |
| _version_ | 1828514995271368704 |
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| author | Lisa H. Tostanoski Yu-Chieh Chiu Joshua M. Gammon Thomas Simon James I. Andorko Jonathan S. Bromberg Christopher M. Jewell |
| author_facet | Lisa H. Tostanoski Yu-Chieh Chiu Joshua M. Gammon Thomas Simon James I. Andorko Jonathan S. Bromberg Christopher M. Jewell |
| author_sort | Lisa H. Tostanoski |
| collection | DOAJ |
| description | Many experimental therapies for autoimmune diseases, such as multiple sclerosis (MS), aim to bias T cells toward tolerogenic phenotypes without broad suppression. However, the link between local signal integration in lymph nodes (LNs) and the specificity of systemic tolerance is not well understood. We used intra-LN injection of polymer particles to study tolerance as a function of signals in the LN microenvironment. In a mouse MS model, intra-LN introduction of encapsulated myelin self-antigen and a regulatory signal (rapamycin) permanently reversed paralysis after one treatment during peak disease. Therapeutic effects were myelin specific, required antigen encapsulation, and were less potent without rapamycin. This efficacy was accompanied by local LN reorganization, reduced inflammation, systemic expansion of regulatory T cells, and reduced T cell infiltration to the CNS. Our findings suggest that local control over signaling in distinct LNs can promote cell types and functions that drive tolerance that is systemic but antigen specific. |
| first_indexed | 2024-12-11T18:07:22Z |
| format | Article |
| id | doaj.art-a7452be5a5f8404eb1b27369c79b3792 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T18:07:22Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a7452be5a5f8404eb1b27369c79b37922022-12-22T00:55:41ZengElsevierCell Reports2211-12472016-09-0116112940295210.1016/j.celrep.2016.08.033Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen SpecificLisa H. Tostanoski0Yu-Chieh Chiu1Joshua M. Gammon2Thomas Simon3James I. Andorko4Jonathan S. Bromberg5Christopher M. Jewell6Fischell Department of Bioengineering, University of Maryland, 8228 Paint Branch Drive, College Park, MD 20742, USAFischell Department of Bioengineering, University of Maryland, 8228 Paint Branch Drive, College Park, MD 20742, USAFischell Department of Bioengineering, University of Maryland, 8228 Paint Branch Drive, College Park, MD 20742, USADepartment of Surgery, University of Maryland School of Medicine, 29 South Greene Street, Baltimore, MD 21201, USAFischell Department of Bioengineering, University of Maryland, 8228 Paint Branch Drive, College Park, MD 20742, USADepartment of Surgery, University of Maryland School of Medicine, 29 South Greene Street, Baltimore, MD 21201, USAFischell Department of Bioengineering, University of Maryland, 8228 Paint Branch Drive, College Park, MD 20742, USAMany experimental therapies for autoimmune diseases, such as multiple sclerosis (MS), aim to bias T cells toward tolerogenic phenotypes without broad suppression. However, the link between local signal integration in lymph nodes (LNs) and the specificity of systemic tolerance is not well understood. We used intra-LN injection of polymer particles to study tolerance as a function of signals in the LN microenvironment. In a mouse MS model, intra-LN introduction of encapsulated myelin self-antigen and a regulatory signal (rapamycin) permanently reversed paralysis after one treatment during peak disease. Therapeutic effects were myelin specific, required antigen encapsulation, and were less potent without rapamycin. This efficacy was accompanied by local LN reorganization, reduced inflammation, systemic expansion of regulatory T cells, and reduced T cell infiltration to the CNS. Our findings suggest that local control over signaling in distinct LNs can promote cell types and functions that drive tolerance that is systemic but antigen specific.http://www.sciencedirect.com/science/article/pii/S221112471631097Xlymph nodeimmune tolerancebiomaterialautoimmunitymicroparticleregulatory T cellvaccinenanoparticleCNSmultiple sclerosis |
| spellingShingle | Lisa H. Tostanoski Yu-Chieh Chiu Joshua M. Gammon Thomas Simon James I. Andorko Jonathan S. Bromberg Christopher M. Jewell Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific Cell Reports lymph node immune tolerance biomaterial autoimmunity microparticle regulatory T cell vaccine nanoparticle CNS multiple sclerosis |
| title | Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific |
| title_full | Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific |
| title_fullStr | Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific |
| title_full_unstemmed | Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific |
| title_short | Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific |
| title_sort | reprogramming the local lymph node microenvironment promotes tolerance that is systemic and antigen specific |
| topic | lymph node immune tolerance biomaterial autoimmunity microparticle regulatory T cell vaccine nanoparticle CNS multiple sclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S221112471631097X |
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