Screening Immunomodulators to Skew the Antigen-Specific Autoimmune Response

Laura Northrup, Bradley P. Sullivan, Brittany L. Hartwell, Aaron Garza, Cory Berkland

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.

Original languageEnglish (US)
Pages (from-to)66-80
Number of pages15
JournalMolecular pharmaceutics
Volume14
Issue number1
DOIs
StatePublished - Jan 3 2017
Externally publishedYes

Bibliographical note

Funding Information:
L.N. was supported by the American Foundation for Pharmaceutical Education (AFPE) Pre-Doctoral Fellowship in Clinical Pharmaceutical Science and the American Association of Pharmaceutical Scientists (AAPS) Foundation Graduate Fellowship. B.P.S. was supported by the American Heart Association (AHA) Post-Doctoral Fellowship. B.L.H. was supported by the Madison and Lila Self Graduate Fellowship at the University of Kansas. The authors would also like to acknowledge the Microscopy and Analytic Imaging Core Lab and the Macromolecule and Vaccine Stabilization Center at the University of Kansas for instrument use.

Publisher Copyright:
© 2016 American Chemical Society.

Keywords

  • antigen-specific
  • autoimmune
  • EAE
  • immunomodulators
  • screening
  • splenocytes
  • tolerance
  • tolerogenic adjuvants

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