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

Lisa H Tostanoski1, Yu-Chieh Chiu1, Joshua M Gammon1

  • 1Fischell Department of Bioengineering, University of Maryland, 8228 Paint Branch Drive, College Park, MD 20742, USA.

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|September 15, 2016
PubMed
Summary
This summary is machine-generated.

Local control of immune signals in lymph nodes can induce antigen-specific tolerance for autoimmune diseases like multiple sclerosis (MS). This approach reversed paralysis in a mouse model by promoting regulatory T cells.

Keywords:
CNSautoimmunitybiomaterialimmune tolerancelymph nodemicroparticlemultiple sclerosisnanoparticleregulatory T cellvaccine

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Area of Science:

  • Immunology
  • Neuroimmunology
  • Translational Medicine

Background:

  • Autoimmune diseases like multiple sclerosis (MS) pose challenges for therapies aiming for targeted immune tolerance without broad immunosuppression.
  • The precise mechanisms linking local immune signaling within lymph nodes (LNs) to systemic tolerance specificity remain incompletely understood.

Purpose of the Study:

  • To investigate how local signal integration within LNs influences the induction of antigen-specific systemic tolerance.
  • To evaluate the therapeutic potential of modulating LN microenvironments for treating autoimmune diseases.

Main Methods:

  • Utilized intra-lymph node (LN) injection of polymer particles encapsulating myelin self-antigen and rapamycin in a mouse model of MS.
  • Analyzed LN microenvironment reorganization, immune cell populations (regulatory T cells), and central nervous system (CNS) inflammation.

Main Results:

  • Single intra-LN treatment with encapsulated antigen and rapamycin permanently reversed paralysis in mice during peak MS disease.
  • Therapeutic effects demonstrated myelin specificity, required antigen encapsulation, and were enhanced by rapamycin.
  • Observed local LN structural changes, reduced systemic inflammation, expansion of regulatory T cells, and decreased T cell infiltration into the CNS.

Conclusions:

  • Local modulation of signaling within distinct LNs can effectively promote systemic, antigen-specific tolerance.
  • This strategy offers a potential therapeutic avenue for autoimmune diseases by controlling immune responses at the source.