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

Cell Reports

Thomas Simon¹  Jonathan S. Bromberg¹  Joshua M. Gammon²  Christopher M. Jewell²  James I. Andorko²  Yu-Chieh Chiu²  Lisa H. Tostanoski² 

[1] Department of Surgery, University of Maryland School of Medicine, 29 South Greene Street, Baltimore, MD 21201, USA;Fischell Department of Bioengineering, University of Maryland, 8228 Paint Branch Drive, College Park, MD 20742, USA;

关键词: lymph node;    immune tolerance;    biomaterial;    autoimmunity;    microparticle;    regulatory T cell;    vaccine;    nanoparticle;    CNS;    multiple sclerosis;   

DOI  :  10.1016/j.celrep.2016.08.033

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown