Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific

dc.contributor.authorTostanoski, Lisa H.
dc.contributor.authorChiu, Yu-Chieh
dc.contributor.authorGammon, Joshua M.
dc.contributor.authorSimon, Thomas
dc.contributor.authorAndorko, James I.
dc.contributor.authorBromberg, Jonathan S.
dc.contributor.authorJewell, Christopher M.
dc.date.accessioned2017-08-31T16:40:21Z
dc.date.available2017-08-31T16:40:21Z
dc.date.issued2016-09-13
dc.descriptionPartial funding for Open Access provided by the UMD Libraries Open Access Publishing Fund.en_US
dc.description.abstractMany 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.en_US
dc.identifierhttps://doi.org/10.13016/M2HD7NS84
dc.identifier.citationTostanoski et al., 2016, Cell Reports 16, 2940–2952 September 13, 2016, 2016 The Author(s). http://dx.doi.org/10.1016/j.celrep.2016.08.033en_US
dc.identifier.urihttp://hdl.handle.net/1903/19694
dc.language.isoen_USen_US
dc.publisherCell Pressen_US
dc.relation.isAvailableAtA. James Clark School of Engineeringen_us
dc.relation.isAvailableAtFischell Department of Bioengineeringen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.titleReprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specificen_US
dc.typeArticleen_US

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